ML19220B088

Radiation Insult to Active Bone Marrow as Predicted by Method of Chords. Concludes Method of Chords Permits Rapid Critical Organ Dose Estimation & Helps Circumvent Problems of Relating Organ Dose to Readings from Meters

ML19220B088
Person / Time
Site:	Crane
Issue date:	03/31/1976
From:	Jones T OAK RIDGE NATIONAL LABORATORY
To:
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ML14358A173	List: ML14358A172 ML19220B068 ML19220B070 ML19220B072 ML19220B074 ML19220B076 ML19220B078 ML19220B080 ML19220B082 ML19220B084 ML19220B086 ML19220B088
References
ORNL-TM-5337, NUDOCS 7904250329
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Text

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l Radiation Insult tc the Active Sone Marro.y 14 a s. -=, ~w i +. - mf c n o Pio u' c i C i i s i. D -

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e TABLE CF CC.' CENTS Pace

~

List af Tables........................... fy List of Figures.......................... fy 1

Anstract.

.....1 Intrcducticn to the CHORO Concept.

3 CHORD Applications to Red Ecne Marrcw.

7 CHCRD Di stributien and Marrcw Ceses................

O the r CMCR0 Ap pl i ca ti c n s.....................

21 9

Co n cl u s i c a s............ '...............

23 Ackncwl edg=en ts.........................

24 References............................

25 e

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LIST CF FIGURES Ficure Face 1.

Critical H0=an Cr2an Radiatien Cesi. etry the CHCR0 Ccncept....

4 2.

Distributiens of the Active 3cce Mart:w.

. 5' 3.

CHCR0 Censity Functicns for Active Marr:w in Referen:a Man.

8 4.

Ccse to Active Marr w as Fredicted by the CHCR0 Ccncept.

.11 5.

Active Marecw Ccse Relative to Ex;csure at the Fr:nt of the Chest (A-P Ex;csure)..................

12 6.

Phot:n Attenuatien cf Skeletal Tissue C:::ared to tha' cf Soft Tissue.........................

14 7.

Cose to Ecne Mart:w frc a Bread Beam Incident en a Rc...<ng u.an.._

.....................te e.

-,.e

...a

, tl i.nns...u.e n.,.<,<,

.u..,....a.,.,.:., a... s.

z..

n...

8.

u by the CHCR0 Cgncept.

..................20 Critical Human Cr;an Radiatien Ocsi:eter..........

22 9.

L1Ts C.....

e sn: -:

Tabl e Pace 1.

CHCRC ;(4}t4 Values f:r Active Marrcw in Raferer.ce Man...

9 2.

Active Marrea Ocse Relative te Ocse at the Fr:n of

.a.e C.w.. s............................

.t.e 3.

Ccsa t: Active Marrcw ' rem.'teutr:n Fr:ducad Rac:fi : ens as Predictad by CHCRD Di stributiens.............

19

• f%

t, d 4

t, e

• • Eb

h CRITICAL HUMAlt CRCAtt RACIATIC1 CCSI."ETRY FCP. THE nC,s.T... 3 CLe.,.,.,. s.

• n

.r-.

Abstrac

-.ritical.Ht:an.O.rgan Radi a tion Cesicotry (CSCRO) probabili ty C

density functi:ns for A-7, P-A, bilateral, re:2ti nal, and isc re:ic incidenca, plus simple depth-d:sa data, ;ermit the rapid esti=ati:n of the radiatien insult :: :he active red 5:ne marr:w systac of the ICEF Reference Man.

The CMCR0 c:n = e;t" falicw: the varia f:ns in the

=icr:sc:pic precasses Of abscr;ti:n, attanuation, and sea;:aring en a

=acresc pic level s: that it is not necessary tc atten;: detail ed calculatiens-fer each and every case af interest. Sicilar techniques have been appl'ied te react:r criticality calculations and tha gene al Icgic of the CHCR0 pr: cess can be a:; lied :: any cause-res; nsa type situati:n which can be described in terms Of variatica with distanca in the medic: f intarest. C ses :: active bene carr:a fr = ex::sures t: ph:::ns and neutr:ns are ;re s an tad and ex: ail an t agree at wa:

found with the few available ex;erimental.esults.

Intr:ductien t: the CMcEC C:nce :

When a bicergant s: is subjectad :: a radiatien envir r. ent, a critical Organ er regien cf greates: risk usually is i rradia:ad n n-unifor:1y if the linear dimensi ns :f ne critical Organ are n : scali er "...e d.ao 5.#.

... e.. i. 3..' '..- - :... w... 4.....' e

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s.. s.. -.,n.f....a.s.,.,. g u.s,.1

. u.

1.., a. :. 2. :. -

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a.

...r Radiatien in:uit specific analysas tre usualiv based :n d se :: :eils,

'Resear h s::nscred by ne 'nergy Resea.-:5 and Cevei ::ar: 4dminis tra-tien under ::ntrac with Union Ca. tida C:r;crati:n.

t 'sJg 153

- u

O 4

2 a s all target site er cluster of cells within an Organ such as the mandible, Or a cen er such as the central nerv:Us, er active bene marr w systa=.

.rce scre effe :s, ce:ls r sensitive sites within cells may n:: be irradiated unif:r 1y Lecause Of discrete energy i ss events and micr:d: size:ric c:nsiderattens (?.ssi, 197-) may be desirable.

On a : re macr:se:;f: scale, chr:ni: effects such as bene sar:::as er even leukemia may, in s e ca:as, be dire :ly related t:

highly locali:ed ex: sures such as usually en:: entered in radicthera;y Of tue rs and the maxiet: abscrbed d sa at a parti:ular site (cass Of a gra= as :;;: sed :: an intercellular site) tay be : Ore =eaningful

.w,1

'"e

...a.=.1 a k s. T"..= d.

a.s4

'.: ' %. e w.-... 'l =...=.=.. #. v a.

.....,.w s,y s..=...

-=---

('.!il sen and Carru the rs,

19c2; A.

R.

Jones, 1975).

Catail ed distribu'i:n Of phat:h d:sa to specifi.c active marr:w regicas for A-F, P-A, rotatienal, and side (latar:1) incidence have been published and shculd be readil.e a:; lied :: cany situations of interest (Jenes

_et

_a _',.. 1. 0 7 ',

C'i i '. #... ".

a.a.d. ' Fa. y,

• 0. / " j.

v'

.. r - = d. i.= '.'.. n,.-..=.. d. c n a.a. d.

u risk analyses frem acute effects and these chr:nic effects where risk is thcught :: be pr:;crticnal

the insul: :: the sys e such as usually assumed f r leukemia, it is eften net ::ssibia :r desirable ::

e s '..' " I '. s.'. '... s " 'i. - r*..<... s a., a. c... =. 'i a. #.

.. s., a

.#....s.-~i. l a.va. l.

Therefo r2, it bec: es necessary :: assign a *:ean' insul: er risk :=

a ncn-unif:rnly irradia:ed *:ritical crgan'.

Cne 4;;rcach ::. the d:sitetry of a n n-unif:r:ly irradiated critical cr;an, such as the red bene rar-:w systen, is :: use-a

r. u. a. 5. a...,.. c

a. i...,

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a'..,v <.. a.. '. :c.-.

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cbtained by assuming that the cri:ical Organ is simply a volume of constant density, and for each differential unit Of mass d, chesen by Monte Carl: techniques, the minimu= distance 4 to the closes:

irradiated air-tissue interface is uniquely determined. This pr: cess is c:ntinued until p (4) d4

.i s well kn:wn statistically. Cherd usually implies a straight line thr ugh two ;cints en the surface, e.g.,

the skin; hcwever, in this paper CMCR0 is an acr:ny= derived fr:: C.ritical _H.u=an C.r=an Radia:ica C size:ry and re: resents only a specific percica cf a "true Chcrd". The CMCRC c:ncept is il'ustrated in Figure 1 and the CECR0 cc ;{4}

d4 di s tribu ti:n ;revides

" weighting" factors for an integration ever a spacific insult such as a "aultic:llisten" depth-d:se curve for the scurce secretry cf inte res t.

CHORD Acclicatiens t: Red 5cne Marrew Figure 2 illustrates the dirtribu tt en of the active red bene

= art:w in the ner:a1 adult and :ne c:rres:ending analec f:r zur Mente Caric trans;cr: c:de.

In the adult reference can (IC29,1975) there are 15C0 grt=s of active red marrcw and 15CO gerns of yell w carr:w which art pred: ina:aly ft: cells.

. Inactive yelicw =arr:w cay te transf:rced quickly in:: active narr:w by a stimulus such as bleedi ;

or infectica; yellcw rarr:w in bene shafts is kn:wn :: c:ntain sc e active cells hut, in generai, the ;rceertien of active : ells in adul yellow marr:w is usually ::nsidered :: he small (5; firs,1955). Thu s,

fer nes: si tua ti:ns cf interest, only the ~ red marr:w.aceives maf:r c:nsiderati:n.

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The importarce of a risk esti.. ate based n radi$:fon damage ::

the active marr:w systa= cannet be Overstated as bene =arr:w damage usually will be t.!.e majer ::chanism in radiatien dea th and acute radiation sickness s:e=:ing fr = whole b:dy irradiatien because it cccurs,at much icwer levels (Facey,1953; Wald,1975) than dea h. cr incapacita:ica due :: radiati:n damage of the gut =;;;sa er the central nervous system. For sublethal criticality ac:iden; ex; stre

levels, levels of in:erest in radia:icn pre:ectien, and scpulati:n ex;:sure leveis, :he : st daeanding rec::=anda:i:ns :f :he IC.t; (1964) relate t: the maximu= ;ermissible desas := the, ganads and :he blecc-fe rr.ing crgans.,

In radia tion ;r::acti:n, the tastas are usually censidered t: be the critic 51 crgan of ;rimary interes t because of their shallow iccatien and because of the difficul:y of estimating the bene marr:w insult; h wever, if the ex; sure level subjects an individual t: c:nsiderable risk, then an estimatien of the insul: ::

his active narr w systa= c:uid be advan:ageous f:r datartining wha redicai treat:an shculd be ad=ints:cred pr::;;iy (Wald,1975).

The d se at a penetra icn de;;h of 5 cr. is often thesen ::

describe the insuit :: the red bene mart w; h wever, f:r phet:n irradiati:n the "5 en rule is f tan in errer by a fact:r Of wc and is ex;ected t: be even worse f:r neutren irradia:fon.

This appr:xt:atien tands :: re:ain ;c;ularity in s;f ts of i ts inac:uracy, because the red carr:w is distributad widely in :he skele::n. The skeletal distributi:n sh wn in Figure 2 illustra:es the fae: that, in Seneral, ce specific depth :an be a: piled f:r differen e.::sure 4G8 tJ y _,, e

7 dif3rren

,gccmetries and different irnadiating

a.-ti cl es er even energies of particles having the same na ure.

For internal desize:ry, es;ecially for radienuclides de:: sited in er near the skele ton, a precisa calculati: cal anal:q Of the active

rrew system requires sc=e postula:icas abcut. cavity si:e variatien and the distributicn of these carrow cavities within the skelet:n.

Hcwever, f:r : st situati:ns Of external ex;:sure, the active marr:w cay be assumad to be uniformly dep si:ed in certain regi:ns :f the skelet:n.

This simplificatica is ;ssible because f:r external ex;csure, distance versus insult (desa} variatica is much less than for internal radienuclide de; cst:ica where the insui (dese) usually varies even ::re rapidly than inversely with :.}e square of the distance. {here are two c;; sing effects taa also influence the pheten abscrued d:se t: =arr:w.

These effec s are the increisad s.h 1' =. l d '... '.v "....= '. n e s '. ". c.".. =. =.. "..'. e

a. n."..>...-.= n. : '. c' - +.=,. a.= -

'..a

...e.s e.. r-...S. e r s,

w e. 3... r...... j n....,

%.....e.s... (e i...s.

3....:.,

"a i ; 3 w.,

w w

-r 1952).

As demens:ratad l a':ar,

the ne: influance of these :;:: sing

. e. e., e... 12,,..1 c..,. s < s. e..s.

s.e s..~,,i l

e...

.x. o r... t alth Egh such is ne: always the case f:r intarnal emit::rs.

CMCR0 Di stributien and."a r-:s ~ s es Figure 3 and Tabla i presen: CMC?.C densi:y functi:ns f:r act.ive carr w in the Reference Man Phant:m (!CI?, 1975) f:r A-?,

C -A,

bil.m * =-$ 1

-...=.#. w n a l,

2.- d. is

..-.y.- =...-e."..*..

.. - *..."-.=.n.=...-a.

3

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g...

6

.m..q q p g X.m. g s s O..b. g.

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e.

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r

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C*-:0 0 Cer.si ty u:::i:ns fer Active M2.r:w i: Rafere ca Man.

f-- 6 ?

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Table 1.

CHCRC p(4}d. '/alues for Active Marr0w in Reference Man.

t (cm)

Rouuorui ev A.P n

P.A cv 32atust cv 13ouspic o

a 0-4.5

.00313 6

406:5 3

40713 3

04133 m3!

3 0.5-1 4173 3

4137 5 32 1

IA:0 1

.0533 2

1-2 4603 2

4412' 2

4715 1

J13 1

J34 2

2-3 4308 3

4361 4791 1

214 1

J:S 2

3--4

.3463 3

.3340

.c330 1

.110 1

4944 4-3

.3303 3

444:

2 207 1

.133 1

.132 2

3-4 466:

4730 1

J:S 1

J73 1

J;9 6-7 4744 2

4731 1

JC9 1

J60 J 36 7-4 4703 2

4 743 1

4305 1

4966 1

4336 3-9 4703 4733 1

4735 1

4339 2

.3103 5

9 -10

.0603

.0641 1

.C5 6 1

40633 4

10-11 4432 3

.3 s *.

1

.0440 11-12

.0330 3

.0344 M07 12-13

.0311 3

M9:

4127 3

13 - 14 M92 3

4349 1

.01 1 3

14-13 m32 3

4533 1

.3119 3

13-16 M53 4

4673 1

.31:3 3

16-17 m33 3

4643 1

.0129 3

17-13 m!3 3

.C492 1

.0130 3

13-19 M37 4

.3231

.0134 3

19 *3 4241 '

4 4139 3

4163

• 0-21

.0213 4

• 1-22

.3159 4

• -23

.3133 3

• 3 -24 40913 6

24 *3 403S6 6

15 - :6 40737 7

15 - 27 4067 7

27 - 3 40599 7

23 - ;9

• 0343 3

29 - 30

.0036 3

~.4 -31 40333 9

31-32 40275 11 32-33 40194 13 33-34 40170 14 34 - 33 40147 13 33-36

.00134 14 34-37

.001:5 15 37 - 33 40154 14 33-39 200933 19 39-40 4CO:41 32

• C.sdCeder.t at' varadon ::

e- ::.t.

'i3 1G1

&W ex; sure ce::e: ries.

The peak at 2 c= for r: ati:nal and is r:pic ex; sure is due :: the sher:er penetrati:n dis:ances ta the side ribs and up;er are benes while the : Ore i ;;r:an: ;eak at about 5 c: is pred::inantly fr:b the vertebrae and pelvis. The CHCRC dis:ribu:icns are influenced strongly by the pelvic regica and the thoracic vertebrae which c:ntain ab ut 250 and 255, respec:ively. Of the :::a1 active ma rr:w.

!n Figure 3,

4 varies :: 40 c= f:r r::ational ex; sure because it was assu=:d tha: re ational CMCRC dese estica:es

..r.1T,...,1

.s.

w-

.w,,i..e. <.... w..,s x.e.. s.,.w u..

s,.,

s

.r

... <... s W.11

.e w

is :r:;ic ex; sures, 4 varies :: 10 cn becausa de;;h-4:se data is ex;ectad :: be rela:ed :: the minimu.

distance :: the closes:

1 r., s. e.

.. s. s...e. a.

o.

The CHCRC distributi:ns fr : Figure 3 were used in c:njunction with depth-desa curves'(see Figure 1) at::rding ::

C (~r

. a r'..r D

n s

re mar ~ u

._.a

~

z becausa all CMCRC distributi:ns were n:rrali:ed :: unity. ph:::n desa t: the active = art:w as ;redictad by the CHCRC ::ncep; is shewn in Figure 4; hcwever, bilateral and r: a:i:nal resul ts are net shewn because f clcse agreement with the.'esult: f r A-P ex;;sure.

Figure 5 pr:vides active marr:w d:se relative :: ex;:sure a: the fron: Of the ches: for A-7 incidance.

Alun J nes' ex;e ri.me n tal results (1952) are included and :he ::an devia:ica ber een the 2,c

..... e v. 7

.+a.1 n <.,

.w. e. 3.. 1a..

. s. e w._...,

r.,

....s.s ts n1, e

...4.

r

,. <y.. g g + o 4U

.L. U dar

. f _. 70

4-C R N L-C'.'t G 7 5 -!! 6 5 0 10-a 1

l I llilll l

i l l illil 1 l l llc 5

f, sV,

2-

'/

• /

10-s-a

~

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C

~

Cg P-A EX?CSUREg E

A-P EXPOSURE %

/*

ag10-40 P_

c

=

=

/s'//

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E a

ISOTRO?!C EX?OSURE 2

e

~

io-H..__.

_a 5

2 I

I I IIIIII I

I I I IIIII I

I I I IIII toH2 10' 2

5 10 2

5 10 2

5 (O '

2 3

PHOTCN ENERGY (kev)

Fig. 4.

C:sa to Active Marr:a as Predicted by the 3CE3 '=ce:t.

73. ~163 8

m 9

I in rn O

O, 1

I I

I e

- e n

I n

o o

m m

V~

u W

c e

a e

c 3

a e

a 3

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3 N

t.

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ga z

y w

l r

a @C,

w s-nu O

~

-u 2

un o

=m H m

}-

eE W w Q o O O o -s 2-z c

~

o@

5 C

u-s O e' z.

-a a

u o<

1. 5 o

o Du N

u.=

m e,

i 1

1 I

o O.

c3 C.

v.

N.

O O

O O

O U G6 }U GCJ / Sp C.:

'.,d.a ss

'i f-74.

e.

o 4.

is i...r.d

d. '. -. 's e -v a.

.= s

,' i d. e 1 4... e <. - -

shcwt in Figura 5.

F i,,.. r e.

o applications of the eth:d of C:4CRCs t: critical regi ns in or near bene tiisue.

Ex;erimental results

..e re not available fer higher energies.

Colu=n ? in Table 2 rel esent:

estimates fr:= the C:-iCRC methed' and celu n 5 is frert cur Pcnte Caric transpcrt c:de (Jcnes, et

_al.,1973). These values she.,n in ::leen 5 were calculated at the ti=e of the citad referance but have nct been published previ:usly in this form. The Mente Carlo results shew ex:ellent agreement in the phot: electric regi n (see Figure 5) but seem to bec:ce increasingly

~~., 4. s "... a. x, a....= d.

c.". >. - =.. '..= - i s. i. w-e #.

i. a c.". =. '..a i.. '..". a w.-....n s.#..n.

t

...e......= C= -I c. a.s ".l.a-d.= ". #. =. s a. n-el.a.. a '.'...n a '. ' 5 f s. '... = '. u.,..'..=

a. '. '. =...

.w v

• will be investigated.

f.T....

. C *. j./

...s r

..e,

• he

4...., r *.2n *..

r,.

4.,.

,,se as..s s.3 *0

m. 3 I

b r.a d '. a.=.,.

f... #. d.a...=.n,= c.... s..n *.1.v

r. '..' 4.13

,- h a.n.... i. s e..'.".'

i...

<,..a 7.

r,.e <_en,1

... l u,

e. -..t.,. l s n

.,.a.

r,

6.

, ( 4.c.. - 3,

c, m.....

.3 Alun Jcnes (1954), and Facey (195c) may have suffered slight 6...

all r..

...s./.

3.

• , w d t, e.1

,a..

4.

s s....

.c

.p l e...<

....3 n0r-.ali:ed t: the same ordinate at 25C '<eV.

Much c:ncern has been L

. g r.$a.gd.

\\.:" v... y

10..c9, a au.

...i.

c.

e.

. h.a 6...

2...,

1 4 s s.

-s

.ru a..

n

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' '. e. d. 4 'J h = *..". a.. i '. C....-" I.d

=.. =. ' <

a'..='.-".'.P.". kaY c.2 u.'..=>.

Ca. -." S. a. s

(

n c

a t.,.... C. a s

(' *. 0 #..*. 'J.'6.. a d i ".. s. *. *.... s.'. a r *. *... V =.

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.. s #..#,S.. =. d.

^'=

w 6.0 e n *. - :.V

1. . =. '2 '."=. d. ' '. #,.1

'., #. '..h. #...

' '.. =

.i'..=....*.~..

2.,. s

• 6...

3. 2

~.

.6..,.

...s.

r

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, r. g w...

6. 3

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• 4

/.*a,*..

$ y s. 3. 3..t -....;

n.

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Photon Attenuation of Skeletal Tissue Compared to the. of j

Soft Tissue.

k Ca e,

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gig,tt grow cose neintive to.cose at uie Front or Taue 2.

li If

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T. D. J0tlES, llEALTil PilYSICS,1973, VOL. 2II, P. 2118.

~'"'~ ALCULATED AT TIl4E OF llEALTil PilYSICS, VOL. 211, P. 2118,1973, BUT C

UllPilllLISilED.

CO i&

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f a

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W'LSCN AND CA. RUTHERS C

1

.i

..=- u.i z e

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I"nLo-rv s

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/

/i // i i i i i i r i

i i rrrti i

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PHCTON ENERGY (kaV)

Fig. 7.

Cese :: Sene Ma.r:w f.: a 3r:ad 3 ear :nciden: en a Rotating Phant:c.

9 e

f

• 4 e

f.74

,.3 1gg

At this time.

1: seems : re pr:babie tha: :he di fferen: shapes are due primarily :: the fae: that if one c:nsiders the shape of the curve describing the rati Of the ph:::n luence per unit exposure as a functi:n of ph:::n energy (F.ad. Realth Hbk 197C; Fair, 1957) then cus have a shape that peaks abcut ICC kev the dese. response curve because the fluenca per unit exposure varies Ore rapidly with energy than does the absorbed dose *: the cart:w, and sec:ndarily to the fac:

that 'rliisan and Carruthars assu=ed that 50% cf the active carrcw received a dose similar to that casured in the thoracic vertabrae and 40: received a dose similar :: tha: measured in the sternu=*.

The in ex: allent agreement with Facay's results.(!?!8),

CSCF.D desas are except f:r a cenistant 12% ove-estimat: n.

tais deviatica is

h. a. #..= c '.s ' '. 3 *.=

1'..*i"

..k.a. ac.#.<a....=...w *. s *, n..'. e a t'.. d. ' '2 '..= d.

'a o

skull (see Figure 2) which Fa:ay did r.0 0 inciude, (b) ex;aricental results f c=

Facey appear :: have been ner.2ii:ed :: Other experimental resuits at 250 key, (c) ex;eri:entally Ob:ained d:ses systa= r.ecessitata the assu=pti:n :f an " effec:f ve the active

a.. ;.d

.,,. w

n... n, i.,, We 'a < :. :.. r.

.a

... y.,

..a s s w..n,., r = n :.,, s.

t.....-..,,..

, ~t i g <.7

c....., g e,.a

,gsc)n.,ng (.> )

. u.,

.e :e...., a. <.. z.,..

.a u..

2 attanuation by bene tissue shielding *he marr:w.

• s seen fi Ff;ure 5, This methed of averaging wculd tend t: underesticata d:se at 10-er energies heause as Facay (1955) ;cin:s cut, the *:eivis d:=ina

=.s d.e s.a 2 '. h i -'.e r.

=... = r i a. e.

..1 1 ~a e. ' v.. =.

...-.=..#.-. v =....= ^. r.= =.... s a -

3 s

rum de-n :: 20 kel. There

..e ribs en er sec:nd : ace an: :el:w 2C kaV

'. ' s

.. i.. =..=. *

,ac.ev (. : :... '> a...=..... -

-=.e.

'..s

-.#dd..-

,. <. = s in the r::ati nal case and '.is results are sh:on f r. Figure 7.

c '. '. '.. a 'e =.

".. ". a i :.~. = '. "

... '. s

• e ". =.. 4. e a.

..a s 2 s.=',.'.=.'-

.r.

.<..,,,.,.'. s..se e.,,.4.,.<,

, r,.. 4,. <.,

.u s

2....

y 7....e a, c.....

...s..a w..........

'.~ eve,

s. =. -.

'..=~...=#.s

=.. =. 5 e. -,. -

~~...-...u.,

-=.....i..

e h

V3~1E9

this effect is rot lar-. except f:r extremely low energies.

At Ehe icw

energies,

e :: the shall w marr:w bec: es increasingly i ;crtant, as is ;newn by the rapid attanuation Of dose as a func:icn of depth, and Ics: ex;erimental results are ex;ected :: be somewhat icw because of the rathed of averaging.

CHCR0 d:se values were normalized per unit ex;;sure ac: rding :

the P.ad. Heal th Mdhk.

(1970)".

In spite Of fact:rs a, b, c, and d, excellent agreement f:r b.

A-P a.s *.'..= *..= s ( n'. R.

w'.a.e s,

i.c. e.a )

and.

r a. *..'.4.

.. ' 'i a s '. i.'..= s. (.~.>.a..v.

1963) c: pared wi:n the method of CHORCs is :: served.

Figure 1, which shcws the d=sa to the active marr:w for ex; sure : Icncenergetic 9

ph: tens, sugges s that if one is c:ncerned :nly abeu-pretacti:n of

.his bene =arr:w, he sh:uld nc: de the instin :ive thing and turn his back, but instead sh uld face the hazard while backing away. The same effect was ais: observed by Piesch (1963) and h ids fr the neu.r:n data in Table 3 which illustrates d:se t: the active carr:w fr :

ex;csure : rencenergatic neutrens. I::e af the data in Table 3 are plettad in Figure 3 f:r ease.cf a;;itcatien. Silateral and rotational re:ul ts are not shewn in Figure a because of their class agree =en:

wi th tha resul ts fr A-P ex; sure.

Abs:rted dose fr : nau:ren pr:duced reccii i:ns is usually charactari:ed by the hydr: gen at::i:

density, because ab:ut 705 :( the abscrbed desa is due :: intera:: ices with hydr: gen at::s f r neutr:n energies belcw 11 Ma'l (Auxicr, 1953; Jcnes, 1974).

S tandard s ft cus:Te tissue ::ntains abeu: 10% by

.?: sten's ::nver sica values of fluence er unit ex:csure f:r One Ref-

. 't. -......31 r"..,-e. =.<., =.,"..> I

> 1 s_-..si.3. n.>.., '.-.

e...c.o p.,

.4. s u a.

2 y

t: those in the Rad. Heal th Handteck.

f 9

y W,,

,,.- 4 r

=

,1 t

e Table 3.

Dose to Active liarrow from tieutron Produced Recoil Ions as Predicted by C110RD Distributions.

FREE-SPACE" g

EllERGY.

KERMA P-A

A-P llILATERAL ROTATI0llAL ISOTROPIC

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{0 10 NEUTRON ENERGY (kev)

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x

... ~

f' Cose from flecoil Ions to tlie Active Harrow as Predicted

-d flg. 8.

N-by the Cit 0ftD Conceint.

N e

e 1

21 weight hydr: gen and has a specific gravity of' unity, while bone tissue c:ntains ebcut ene-half the weight percentage of hydr: gen as does cuscle dissue but has abcut twice the specific gravity of ruscle tissue se that the hydr: gen ata=f e density is not very different for the twc types of bicicgical tiss0e.

Lung tissue has a specific gravity of enly abcut 0.3 and the hydrogen at:=ic density, theref:re, is quite different; hewever, = cst critical crgans of interest are either distant fr = the lung tissue er cicser to an irradiatad surface 2

se that the penetraticn distance in grams /ca is less than the other

crtien cf the ray cf travel tha't passes thr

ugh a section of the lungs.

Based en, dep th-dese curves frc= s me of cur previous

~

calculaticns (Jcnes _et _al.,1973), it is believed that ::s reaicns of variable. specific gravity de act significantly influence the applicatien cf the mathed c,f CHCRCs, unless cne is s;ecifically interestad in desa to a vcluca cf lung tissue.

Other CMCRC 1 clicatiens Figure 9 illusti?tas a pre;: sed desi star r " risk =atar* in which the relative settings of the cutar tac dials select the a;;rc;riata CHCRD distributien and the inner twc dials select the insult (decth-dese) curve f:r the energy and type of incident radiatien. Alun Jcnes (1965) suggestad that desicetry should be appr: ached by matching variaticas 'in d:se ce risk wi th scattaring, abscr;ti:n,

and

. a ttanuatien; hcwever, the CECRC :s th:d see : :: pereit this same precisi:n Of matching variability :n a sic;1ified acr:se:;i: level.

Hccefully a sche:a such as inc:r; ratad lat: Fi.gure 9 wculd rendar the abscr' ed d:se index, 3 ;, and d:se ecuivaler.: index, H.,

f:r t

9-iv;3'L13..

_f a

Ce

.2M OtRECC3 CF T'nt LELAT!YE mt?'C1 CETERMt.NE3 THE COR.tEC P(f.) OthiR11r%TIGN 43*

CR1ENTA?!ON 08AL 410 MAAACW g

CRCA%

O g

/f THE 4ELAIIVE PCMITIC'8 t

f g'cek.

g g

g d

OETE MM t.N ES T H E C*J A A EC g

y E.

D (1) Rt37213uTIGs y%

E.N E t CY f

3EuTRC.,

/!

,Ad T

f

/

l f

3 3

h

=Ac:2r:C3,

e TY PE

/

C a

/

rs

= w ave

.cr-

>+;.

~>

n

.e +

he.$

r r

3

~'O

'/

g PRC5} Art l'

9.,

., %,\\

/

~ =.2 eam

/

%o j

- \\

M

!=-

rs ggTH,A THE CHORD METER d

/

\\

/

T N

,/

g

.\\

s

/

N N

/

N

/

CVI.*u!CE CpnCNS N

/

N CRIENTAECN SPEC 3UM C W A r Ass:C s' n 3RCAO SE.ut L E.A A AC E.:liS;CN C, + A L T t TU C I N A L 9 s.4 A.t C w S E.ut,9 s""' T!! E R.v CN UC*.J A R " l.N TIC RA 7; I

r" RESIT IE?C M C R 120.N TA L ~~ ISCTRC P'C C 2 - 15CTRCPtC CC05M'C

~

Fig. 9.

Critical Mc=an Organ Radiation Cesiretar.

o

, Me h3*...

1 e

9. p.

,v^. -.. s..a. a. =. *.:.". 10. / '. ) a.v a.n l =. s e "s a'. u l

• ".> 1 t.". e * * '. ~d $.

d.

t u.s.

already is, because by using CF F.0 densi:y func:icns plus s:andard insult (multiccilisicn des:h-dese) curves, a health physicis: cr Cedical technician could easily and quickly estimate ex;csure values to any bicicgical tissue at risk.

It is aisc beccaing appa ren t that significant calculational an experimen:21 efferts will scen be d

directed to the es:imaticn of tissue risk due to micrcwave irradia ticr.s and the availability of p(4' d!. distribu:icns shculd ::e he,sp. l.

u Cenclusiens I n s e:. a /..". =..~= '.."..d

". r..".

=.,3..- -=~...;..2 r.1. '..' . - i. '...s *i cr3an"

..- d.

ha,l.s

..- c i.-. "... / =....

<m-.~-

. ". =. -.. 'sI =...s c.se e s '. '.....= '. d.....

i p

i

.......... ar

e. t ' a k.a.:.3 s.

po.l g.j riv.-:.,.3 s..a c., a,,r ej2k.

-.as.4.u-:g

.s

.-.a 6i A.. r,....., t.

.s s. _....

_e.,s.,,s......... *s.e s... e..,c.

i..

.ies..,

.,.2..

w.

the reasured execsure car-es;cnds neither to th'e ex;csure in free

..,... s.. s <...~.,. s

.n.. t o sc./.

c., s a. ~.e w

s

.w.

s,. a r.

.......3.

.~.

de * =.....#....=..q '../

1. ..=.=.

s *. a..=

=.x y. s u -a.

' O '. a..e - "., 1 0. '. < ).

."s.'.. w'e n'.s

(*. #.,

s.

3.. t./.

....r

, r,...y,, I.;.-, 1.............~/,

eq),.

2. 3. s w.

.w,.

3 A..

~

.. -.w ".v m -.

.... s ". I.... '..'..=.' '.' #. v a.

., v a.. =. s. #.....*...=

'"a

=

.s s. a. #. 2. 'i.v '.s..a.. ". =.... r = >."..>. #.

.7 i

'.'.d a r a. s. <.. 2 =

".y

.=

'..'c..--

'.a.

w.a..,,.

...n s.s.el u, er

..r

...s..

. u.r

.,a.

..,, <..~...,s s.a,t ;i n -

.n 3

a other than A-P, it is usually very difficult to have an accura's risk

......n1o,.,,....,............

..s.es. -, a. i.. -

. s. : _,.. w... s. o <......., t <6 e.

2....

..... i r,. c.,. 4.

. e.

w.

, a. s.

6.,*.x.

3..

w 73-175

-73

w

(. 9

=

Acknewlede enss This, aper is heavily dependent upon she ex;ericePtal "crk cf Wilsen, Carruthers, Facey and Alun Ocnes lcr the discussion of the results and as a means of estimating the validity of the C:iCF.C ccncep t.

It.is aise necessary to ackncwledge the helpful suggestians and data su;;1ied by Alun J:nes and J. 'd. Fest:n.

O O

9, H

O g

l

=

• g h

e O

g j

O f

. N,...,,~(

f r( )

'T-5/

References Cliffced, C.

E., and Facey, R. A.,1970, Health Physics 13, 217.

Facey,R.A.,1953,HealthPhysicsli.557.

Fair, M.,1957, in Princicles of Radiatien ?rctectien, Ed. K. Z. Mcrgan and J. E. Turner, Chap. 3 (Jenn W1 cy anc Sons).

ICRP Publication 5,1954, Recemcendaticas of the International Cc =issicn en Radicicgical Prc:ecticn, (?erga:ca Fress).

ICRP Fublicatien 23, 1975, Rescrt of the Task Grcup cn Referenca Man, (Perga:cn Press).

ICRU Repcrt 19, 1971, Radiaticn Quantities and Units.

ucnes, n. R.,,. s.,, n. r.-, - 2,,, 0.

a Jones, A. R., July 20, 1975, Perscnal' cc==unicatien to T. C. Jcnes.

Jcces T. D., Auxier, J.

A., Snyder, W. S., and Warner, G. G.,1972, Health Physics ji, 2?1.

Piesch, E.,1953, Heal h Physics 15,145.

Posten, J.'W.,1972, Perscnal cc= unica:icn of fluence per unit ex;csure conversica fac:ces fer Referenca !!an tissue cc pesitica.

Radiclogical Health Ha.dbeck,1970, U.S. Cecartmen: cf Health, Educa:icn, 4

and Welfare, Public Health Service Censumer Pretactica and Enviren-

'~-

cental Heal-n Serrica, Reckville, MD.

Spiers, F. W., 1955, Rad. Resaarch 2j,, 52?.

Wald, N.,1975, " Newer Siciegical Indicaters of Radiatica Carage,'

Refresher ccurse given at Annual Mee:ing of Health Physics 5cciety, July 13-17, 1975.

Wilsen, R., and Carruthers, J. A., Hea' th Physics 7, 171, 1952.

F* #) - -,j gVN IU A. 4 [

. c,.

c-

.sa

2/

0. ". '. / 'i...:.'.. -

u o..,.,,.. r !.

I.,h,....,m,,,

...~ i w 1-2.

Central :ese=rc.5 Library 3.

Oce=en: Reference Sac-icn, CRL 4-6.

Labcrat:ry Rec:rds 7.

Labcrat:ry Rec:r:s, CR"L, RC 8.

ORNL Pa:en: Office 9.

J. A. Auxier 10.

J. L. Hwang 11.

D. G. Jacccs 2-1,/.

i. D. v,enes 4

18-22.

G. O. Xerr 2a.

J.

.J. e,cs :n 2 <,.

C. R. Rt,.......a

~

25.

D. X. Trubey ev :... L n.e.x-

n a.3. I 7

.a.... w u...

2: :..

'6=.".."..q'..='.

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David E. Sarnharic, E.:A, Ecx 15027, Las '/acas.

.l 2 11' 61.

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A. 3. Chil :n, Universi y of Illir.cis, L'rbana, IL 4.'/.

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2 28 71. Cesmend R. Cavy, AAEC, HPR Secti n, private Mail Sag, Sutherland H.S.W., Australia 72.

J. A. Cennis, Naticnal Rad. Fret. Scard, Harwell, Berkshire, England

73. Marc H. Caus et, Center d' Etudes Nucleaire, Ce: art:er.: $e is d

Pr: taction Sanitaire, Servic: d' Hygiene At:='. ue, 3.F.S 5

Fcntanay - aux - R:ses, France 74.

R. A. Facey, Cafense Resear:h Establishment, Cefense Rasearch Scard, Ot:awa 4, Canada 75.

S. 3. Field, MRC Cylectr:n Unit, Haar.ersmith Hospital, L:nden, England 75.

5. C. Finch, Radiaticn Effects Research Foundati:n, 5-2 Hijiyama Keen, Hir:shf=a 720, Jacan 77.

N. A. Frigeric, Argence Na:icnal Lab., 97CC Scuth Cass Avenue, Argence, IL 5C439 78.

R. '/. Grif'ith, Lawrence Liver re Lab., University Of Calif:rnia, P. O. 5cx ECS, Liver:cre, CA 94550

79. Ferenc Hajnal, RASL, E.RCA, 375 Hucsen Street, "ew Y:rk, MY 1CCl?

S0. Cale Hankins, 312 Per:rillo Crive, L:s Alames, N t 57544 SI. Tadashi Hashi:u=e, National Institu a of Rac'elegical Sciences, Chiba.2EC, Ja:an

52. William R. Hendee, Ce::. Of Radiolcgy, University Of Celerad Medical Cantar, 420 East Ninth Avenue, Cenver, C lcrado 3C22G 33.

G. H. Herling, Code 5555, Navy Ce:ar en:, Na'tal Research Lab.,

Washing :n, CC,

20390 E4.

H. E. Ing, A::=ic Energy Of Canada, Ltd., Chalk River Nuclear Lab., Chalk River, Ontari XCJ IJO, Canada 35.

H. Jarmat, C:=:issaria: a l'Energie A :=icue, Cantre d' Etudes Nucleatra de Fcntanay - aux - Rosas, France SS.

A. R. Jcnes, Health 7hysics Branch, A:::ic Ener:y of Canada, Ltd., Chalk River Nuclear Lab., Chalk River, Catario KCJ !JC, Canada

37. Cean Kaul, Science A: licatiens, 5005 "ew;crt Crive, Iuite 2C5, Rolling Meadows, IL ECCCS

38. Sadahisa Xawa :::, Racia-ica Effec s Research Foundatica,154 Sakurabata--7.achi, Nacasaki 550, Ja;an 39.

T. J. Kennedy, Jr., Naticnal Acadecy Of Sciencas, Washing :n, CC 2C413

90. Las:lc X blinger, Health ?hysics Ce:., Can:ral Research *nsti-tute fer ?hysics, P. G. Sex 49, 1525 Suda:es:, Hungary

91. Andr:ej Kraf t, Insti:u:e of "uclear Techncicgy, Acadacy Of Mining and Metailurgy, Crac:w, Al. Mickiewic:a 30, P: land

92. Lawrenca H. Lan:1, The Franklin McLean Mee: rial Researen Instituta, Univtrsity of Chica;, 950 E. 59:n Street, Chica;;, IL 5C537 93.

R. C. Lawson, UK~ EA, Cha:elcr:ss, Annen, Sc::' and 94 J. L. Live r=an, USE?.C *, '.!a shi ng::n, CC 2C5 5 DS.

2. Makra, Can:ral Rasearen 'ns i: :e f:r Physic:, Suda:est.I!!,

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P. H. McGinley, Encry University C1inic. De:ar ment of Rad.

Therapy,1355 Cli f::n Rd., M.E., Atlanta. CA 3C322 99-1C3.

I. M. Mariyama, Radia:ica Effects Research Fcundati n, 5-2 Hffiyama Xcen. Hircshima 730, Jacan 109. - Ladisiev Musilek, Technical University of Prague, Faculty of Technical and Nuclear Physics, Erehovd 7 Praha 1, C:ecac-sicvakia 110. Dieter Nachtigall, Stahlenschut:, Eurat:m 2 5KM, Steenweg naar, Retie, Geel/5elgium.

111. Xeren O'5cien, Health and safety Lab., USERCA, New Ycrk, NY 1C014 112.

Ing. F. Fernicka, Laberat:ry f:r Radic1cgical Cosicetry of the Czechosicvak Academy of Sciences, Praha 3, Na Truhlarce 39/2a C:echosicvakia 113.

E. Piesch, Karlsruhe Nuclear Research center, Rad. M: nit: ring Service, Federal Re:ublic of Germany 114.

S. Pretre, Research Instituta f:r Fre: active C nstruction, SC01 Zurich, Swit:erlanc 115.

H. H. Rossi, Pr:fesser of Radi:lcgy, College of Physicians and Surseens of Colu:bia University, 530 West 155th Street, New York, NY 1C022 11 6.

W. J. Russell, Radia-ica Effec:s Resear:h Fcundaticn, 5-2 Hijiya a Keen, Hireshima 720, Ja:an 117.

E. L. Saenger, Racicise:::e Lab., Cincinra:i General Hes: ital and University of Cincinnati College Of Medicine, Cincinna:i, OH 452E7 113.

J. W. Smith, AERE, Harwell, Didc :, 5erks., England 119. Xenji Takeshi a, Research Insti ute for Muclear Medicine and Biolcqy, Hircshima Univerti y, Hircshima 720, Ja:an 120. Arnie Warshawsky, U.S. Army Agency, Fer: 31 i s s, El F asc, TX 121.

O. E. Watt, UKAEA, Chacelcross, Ann:n, Scotiand 122.

F. 5. Willia:s:n, Ciyisi n cf Eiclegical anc Medical Resear:h.

Argonne Naticrai Lab., 97CO 5:u:n Cass Avenue, Ar; nne, IL 5C439 R. Wilsen, Defense R~ searen Cha:ical Latera:Ory, 0::2 a. Canada 123.

e 124.

R. W. Wecd, USERCA, Washing::n, CC 20545 125. Hisac Yamashita, Radiatica Effects Research Fcundation, 5-2 Hijiyama Keen. Hir:shima 720, Ja:an 125.

T. O. Yeung, A::=ic Weasens Resear:3 Es:2blisP:ent, 31dn. A-29.1, Alder:ast:n, Reading RG74PR, Uni:ad Kingd:m

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/

s THE EF:ECTS OF SMALL CCSES CF ICNIZING RADIATION:

FUNCAMENTAL SICPHYSICAL CHARACTERISTICS HARALD H. ROSSI Radiciegical Rasearch laberatory, Colu=:ia (faiversity, Collega of Physicians & Surgecns, New York Ci[y, New Y:rk 10032

/

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3 Nu:-ler of ;: ages:

19 Nu::ter of figures:

5 Nu:-ter of ables:

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Runninc

Title:

Fundamental s;nall dose effects Cor es::endence to:

Dr. Harald H. Ecssi Radiolcgical Research Laboratory

• College of Physicians & Surgeens Colt:bia Unive-sity 630 West 163th St. eet New Ycrk, New York 1C032 e

es e

m o

e e

m O

e e

g

-o-Rcssi, H.H. The Eff is of Small Ccses of Icnizing R

'ation:

Fundamental 3f cphysical vharacteris tics. Radi =

• as.

ASSTRACT i

Frca an applicaticn of the cencepts of =f eredesimetry :: a wide i

i

}

range of radichiclugical data en higher crganisms, it has beccee apparent that the first step in the biclegical action of ionizing radiatien is the j

f inducticn of subcellular lesiens. Two basic characteristics of this process j

1 at that it depends cnly en the first and (sc=etimes) the secend pcwer of the

]

I abscrbed dose and that the yield of such lesicas as well as. te cagnitude of j-I

~

the decain where energy concentritica determines the yield Of lesicas is re-3 l

latively constant even for cells and effects that differ greatly in radio-j i

sensitivity. These cbservaticas have led to the formulatien of the Theory j

t i

of Cual Radiatica Action which ;cstulatas that the yield of these lesiens i

depends en the square of the specific energy in demains having an effective i

dic=etar which differs frc 1 um by much less than an crder of =agnitude.

j

../

t It has further:cre been deduced that lesiens are produced by the inter-g action of pairs of sublesiens which are presumed Oc be alteraticas in C.'tA 3

structure at the nane:eter level.

j There remain many questiens regarding the cuantitative relation w

I cf lesica production to cellula.- injury and the dependenca of multicellular 3

I respenses en cellular impairment. '4hile these uncertainties make it fre-

.J 1

quently impossible to derive explicit dese-effect relaticns, the existing j

i framework permits a variety of general cenclusicas and it may be utilized j

t to cbtain specific answers in scoe c2ses.

j l

An is:crtant exarcle are risk estimates for the inducticn cf t

, he:an leukemia by neutrens. It is cccciudad that maxicum permissible j

I neutron deses cust be reduced.

i 4

Kay pnrases:.necretical radiebicic;y; Raciaticn ;rctecticn; Eisk esticatas.

i V4r h

a-s$3 $

Y

1 The ultimate cbjective of radicbicicgy must certainly be the identi-fication of the intracellular and intercellular alteratiens tlf at are initiated i

by ionizing radiatien and progress to manifest injury. At present we are stili far frca this geal and in what is the mest impercant effect for radiatica i

protection - carcinogenesis - this is in a large measure due tc cur igncrance 4

i cf the biological changes that underly what is probably a complex of diseases.

l Although studies of the action of other carcincgens and biological l[

i advances in general r.ay well be imper' ant :o the achievement of greater I

i insight inta de cancer prcblem, radicbicicgy has the decided advancase l

that it can apply an effective agent to the genetic apparacus directly and accurately. This permits quantitacive experimentaticn which is best carried cut at icw deses where secondary effects are likely to be less impcetant.

The Ocse-Effact peTation 4

An i;ipertant inter ediata scal of theoretical radicbiclocy wcuid 2

j seem to be the establishment of the relatiens bedeen dese and effect which 1

can not only furnisn clues regarding the nature - and especially the kinetics -

)i of radiobielegical effect but also conscitute tha principal objective of radiatten pectacticn.

In either applicatten the precise 'tatues of the relaticn are of lesser i=pertance than the sha;e of the dese-effect curve i

particularly at icw values of the dese where extrapoiaticns are of censider-able scientific and prag.atic i ccrtance..

The shape of the dese-effect curve for individual cells can be stated with a certainty that inc easas with decreasing dese: It b:st 1

ultimately beccee linear regardiess of the energetics of cell inactivatien 1

and regardless or variaticns in sensitivicy of de individuai cells in Se i

ir adiated pcpulaticn. This ccnciusien fcilcws frc the siccle fact dac i

)

V3~184 G- ?2

at sufficiently icw doses the tnversal of a cell by a charged particle is a rare event and the prcbability of multipie traversals is negligible. t:nder these conditions the dese-effect relation must te linear and any effect under censideration must occur with a probability which is in turn the product

~

of the prcbability that a particle causes the effect and the prcbability that a cell is traversed by a particle at the dose under censiderat en.

inis statement can be femally supported by a very general ;rcof (1) and micrc-desicetric data (2) may be used to detamine traversal frequencies.

It can be shewn that the linear dependence must for icw L:.7 radiatica extend up to doses of at least a few hundred millicads.

For neutrens of =cderate energy this limit is of the crder of tens of rads.

These consideraticas can be applied caly to these biclegical effects which arise frca individual ncn-interacting cells. Thus if carci,csenesis were 'to require, the transformation of a grcup of c:ntigucus cells (3), one would expect a dose-effect curve exhibiting a pcsitive curvature. 'Jhile this does not seem t0 have been extablished at icw deses, the reverse conditica Of negative curvature has been clearly de==nstratad for the inducticn of za= ary neoplar:s in the Sprague-Cawley rat (4). Thus in at least ene instance, c.treinesenesis cannot be intar;reted in terns of a simple sc. atic zutation

\\

\\

which results in cancer regardless of the irradiatica of cther celis. Although

\\

the argument applied abcve to single cells can be extended te whatever grcup

),

of cells night be involved, it Icses its practical significance if bis g-cup cc pises scre than a fw cells since extremely minuta doses are required to limit the c:llective inversal ;rebebility for all cells t: a value that is much less than ene.

q'g }$b 4

?- W

The Cesa-RSE Relatten Although collective effects en cells can thus affect the shape of dese-effect' curve they are far less likely to influence the dese-RSE cur <e which is cbtained when the RBE cf a high LET radiatien ic.c: pared at varicus doses of either radiatien (i.e. at various levels of effect). The reascn fer this is presumably that the interacticn between cells is "the sa:e regardless cf radiation quality and that even in cceplex syste=s the dependence of RSE on dose pri=arily reflects differences between the radiaticns under cc: pari-sen in their kinetics cf the impair :ent of individual ccnstituent cells.

Figure la shews the dependence of RSE en the dcse of 0.t3 MeV neutrens for the man:ary neoplas..:s in the Sprague Oawley rat. The bars ccver RBE values that are axcluded with 99". ccnfidence.

('he arrewheads ccrrespond to lesser levels of ccnfidence).

Figure Ib shcws the dese-RSE relaticn fcr the sa=e radiatien but for cpacification of the = urine lens ever a thcusand-feld range of dese (5). The statistical analysis e= ploys ncn-para =etric methcds develeped by Xellerer and Srenct (5).

In either case the REE increases "over a wide range cf desas as the in-verse 'cf the square rect of the neutren dese (as indicated by the slepe of -1/2) to values in excess of 100. This indicates that the biological effectiveness of icw LET radiatica inc eases as the square of dose (2).

Figure 2 c'mtains the curtes in Figure 1 as nell as others which are not based en the ncn-para =et-ic analysis but are never-heless censi-dered to be of sufficient accuracy (cf the ceder of perhaps t Sci). The radiatiens are 0.42 MeV neutrens and "fissicn neutrens.* The latter clacsification is not very specific since the ener;,y spectr.m cf the neutrens re.;hing the hiclegical =aterial cust decend tn yariable and-i I

g_~4gG F er

often uncertain scderation of the primary fission spect um. A calculation 1

,cf. the dose =ean lineal energy (y0 in a 2 m Ussue sphereT indicates a l

value of 55.5 XeV/um for the spectru:n in a reactor irradiation facility utili:ing a mcderated cenverter.3 This particular value differs little frem that for 0.43 MeV neutrens which is 50.5 XeV/;m (7).

All of the curves in Fi;. 2 ex.".ibit the characteristic slope of i

f

-1/2 although two indicate constant RSE at 1cwer doses. Curve 2, which l

represents a sc=atic plant mutation, levels cut near the value postulated by an elecentary application of the theery of dual radiatien action (8).

. Higher RSE values ay be due to differences in the yield of sublesions (9) while possible levelling at icwer R3E values as suggested by curve 3, which relates to survival of cells in tissue culture (10) ceuld be caused by a linear cecpenent of radiation acticn (2). The other curves sacw no evi-1 dence of a cha'nge in sicpe but are limited to c::caratively high doses.

They are based en the results of two determinaticns for chrc csc=e aber-3 rations in human lymphecytes (11), (12). The fer cr deter =inaticn (curve t

l

4) was h vitre at a reacter scurce, the latter is based en late effects in atecic bc b survivors (curve 5). The RSE values are similar. There is 3

in fact far ccre variation in RSE with dose than there is between the varicus systems.

Princical Destulates the above censideraticns may be su:::ari:ed as felicws:

1) It can be shewc.cn ce basis cf ele =entary micredesi: etric censidersticas that, at ext. emely Icw dcses, the direct effect cf icni: int,

.i radiation en individual cells. ust be pre;c.rtional to the dose and te the prcbability eat a singl a charged particle affects Se cell.

It has been cbserved dat this pr bability differs bedeen icw La raciaticn and neutr:ns

~:

1 1

g,j. 4 hrf d

p(

I c_o

/

/ n9

~

having. energies of the order of a few hundred XeV by a factor that is larger

• ~

~

than 10 and can exceed 100.

2) " At intermediate deses, the ASE declines because the effective-n

)

ness of low LET radiation incre ses as the square of the dose.

3) The dose-effect relatien for cell systems can not be deduced frem sicredesimetric considerations but the dese-RSE relaticn r.ay be expected a

to be the same as that for individual cells.

3 i

These pcstulates are insufficient to furnish general answers to nist of the primary questiens in radiatien prctection. Mcwever, whert applied to epideniological data, they yield significant information.

Acolicatica to Radiation leukemecenesis i -

Cae of the principal late radiation effects is leukemia which cccurs i

with clearly increased incidence in the heavily irradiated pcpulation grcups I

';hile in the for=er city, the radiation censisted 3

in Nagasaki ar.d Hiroshima.

almost exclusively of ga==a radiation, there was a substantial ccepenent of d

neutrens in the lattar.

E' M' I, Fig. 3 shsws the logaritfra of incidance over the pericd frca 1950-i d

. ;,, 6 1956 (13) af tar subtraction of the incidence in the grcup that was assumed to have negligible kerma # (less than 5 rad). De abscissa is the icgarida of 7

total tissue ker=a (gama plus neutren) in free air. The uncertainty is such 1

that in either case, a linear relatien (i.e. a'line of sicpe 1) can not be a

rejected (14).

In an applicatica of the ncn-parametric methed illustrated in Fig.1, l

j it could be shewn (15) that'a constant ratic cf bicicgical effectiveness (as 3

4 based en total ke:na) cculd be rejected at a significance level cf 55% and it

)

was ccncluded that the Japanese leukemia data do not constitute an exceptien 3

to the generai ;;cstulate 2) given abcve.

The analysis indicates that a totai ke:- a cf 10 rad at Hireshima

'i3'188 q - 9,

~

1 J

, had appr:ximately the same leuke : genic potential as 70 rad at Nagasaki.

l 1-The REE cf neutrens relative to ga =a rays is cuch larger because at Hireshima only one fifth of this total karma was due to neutrer$s.

In 1

additien, the bcdy tissues surrcunding active :ar Ow attenuate neutrens

=cre effectively than ga=a radiation, the factors being 0.25 and 0.55

'(16).

It fcilews that if the dose to the bene marr w is abcut 0.5 rad 2'

of neutrens and abcut 4 rad of ga=a rays, the same leukemia incidence results as frc a ga=a dose of abcut 35 rad. Even if a linear dese-effect' relation is attributed :: ga=a radiation, it is apparent that at icw deses, the leuke cgenic effect in Hiroshima was al= cst entirely due 1

to neutrens.

Furt$er study has indicated (15).' hat if the dese-effect curve I

consist: cf a if near and a quadratic tern, the far er is negligible for

}

ga=1 radiation'and the latter is negligible for neutrens..Cn the basis

'a cf this finc;rg, it has been c:ncluded that if Cn and Oy are respectively i

the =ean d:ses of neutrens and ga=a rays to the bene carr:w, the annual c

incider.ce cf leukemia (as averaged. cver 15 years) is abcut 5 x 10 ~D 2

n

-8 2

and 1.8 x 10 0 for intervals of 0.5 to 10 rads of Cn and 2.5 to 50 cf Y

a D.

These relations are pictted in Fig. 4 and the ::rrespending RSI re-1 T

3 latien is cu: te 5 in Fig. 2.

1~ne latter appears to be a c:ntinuation of I

J

'he line for chre::sc:a aberraticas.

~

A recent analysis (17), us'ng a sc=ewhat different approach, I

~e yields 3 x 10 ~D for ;he neutmn curve. Mcwever, the diffarence is al-1 a

I

= cst ent'irely due t: the icnger averaging pericd.

I f

A1sc shewn in Fig. 4 are de s;cntanecus leukemia rates at the 1

tao cities and the maximum permissible average annual c:upaticnal dcse i

(."PD) f:r reut on and ga=a radiatica.

f - in-line with cur ent 'hinking -

1 1

73--1E9 9-ff

. it is assumed that, at least at icw doses, there is little effect of neutron dose rate on biological effect, it becomes apparent that one cccupa-tional Mp0 of neut:.ns will for sc e 15 years result in a risk rate that is essentially equal 'a the atural rate. This seems excessive and a sharp reduction of the MPD for neutrons seems indicated. This might best be acccmplished by an increase of the quality factor (Q). On the other hand, no changes seem necessary for the MPO of icw LET radiation which is of far greater practical importance.

It will be acted that Fig. 4 applies to the dese.in the bone narrew. If limits are applied en the basis of ker=a or of the abscrbed dose index, a safety facter of the order of 4 applies.

Cenclusicns Both thecretical radicbiolcgy and radiat.'en epidemiology are

~

beset by limitatiens; the former because of the uncertain generalizations which are the essence of ~inductien; and the latter because of the possi-bility of uncontrolled variables and dosize ry errcrs. These cencerns

=ust be arkedly reduced if thecry and observation yield concordant results.

e The validity of the least square fit to the epidemiological data seems acre assured because it results in a dose-P2E relatien that is similar tc that cbserved in all other systems subjectad to analysis, and. the accuracy of desimetry see=s c be decenstrated by the fact that the absol'ute value of the curve parameters is also cicse tc that fer the other systa=s.

It seems likely that fundamental bic;hysical consideraticas will thus continue to be of ;ractical utility in addition te providing the basis fcr cur ccm-prehensica of radiebiclogical mechanisms.

=

f~ff f f4.80

s c

1 FCOTNOTES j

4 1.

Presentated at the joint :::eeting of the Radiation Research Society and the '4eal th Physics Scciety, San Francisce,1975.

g This investigation was supported by Centract E(ll-1)3243 frem the Energy Research and Cevelo"- 2nt M:ninistration and Grants CA 12526 and CA 15207, awarded by the National Cancer Institute,

)

~

1 CHE'J.

j 2.

Thrcughout this presentation the shortar tam "dase' replaces the cre accurate "abscrbed desa."

s l

3.

Teedia, P,eeter: unpublished data d

4.

In the felicwing 'ker=a" will, for brevity's sake, replace l

9

' tissue kama in free air."

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<l si ACXNCWLECGMENTS The author is indebted to Dr. Eric J. Hall for

-}

g helpful discussicas and to Mr. Peeter Teed 32 for calculations.

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REFERENCES 1.

H.H. Res,si and A.M. Xallerer, Radiation carcinogenesis at icw deses.

Science 175, 200-202 (1972).

2..

A.M. Xellerer and H.H. Rossi, The theory of dual radiation action.

Current Topics in Radiat.Res. Cuarterly 3,35-153 (1972).

3.

G. Failla, consideratiens bearing en permissible accumulated radiaticn doses for cccupational exposure. Radici. 69,. 22-2S (1957).

4.

C.J. Shellabarger, R.C. Brown, A.R. Rac, J.P. Shanley, V.P. Send, A.M. X' llerer, M.H. Rossi, L.J. Gcedman and R.E. Mills, Rat ma==ary a

carcinegenesis fcilewing neutron cr'x-radiation. In Eiclecical Effects cg[ Neutren Irradia tien (!AEA-SM-179/23), pp. 405-415. Internattenal Atemic Energy Agency, Vienna,1974.

5.

J.L. Sateman, H.H. Rossi, A.M. Xalltrer, C.V. Robinsen and V.P. Bond, Case-dependence of fast neutron RSE fer lens cpacificatien in mice.

Radiat. Res. 61, 231-290 (il72).

6.

A.M. Kellerer and J. Brenet, Ncnparametric determinatien of codifying factors 'in radiatien actien. Radiat. Res. 56, 23-39 (1973).

7.

M.H. Stavati, '4. Resen:xeig, H.H. Rossi and I. Miyanaga, The dependence of RSE cn the energy of fast neutrens. III. Evaluations of radiatica quality. Radiac. Res. 19, 512-525 (1963).

3.

A.H. Sparrew, A.G. Underbrink and H.H. Rcssi, Mutacions induced in Tradescantia by millicad deses of x-rays and neutrens: Analysis of dese-response curves. Science 175, 916-913 (1972).

9.

H.H. Rcssi, Neutron raciatien quality. In ? rec. Firs: Svmc. cn Neutren Ccsi etry in Bielcev and Medicine (EUR 4696 d-f-e), pp. 57-71,1972.

5 ?$ ~.

O (u

4...

h * /$ $==

O 10.

E.J. Hall, H.H. Rossi, A.M. Xellerer, L. Good =an and S. Marine, Radiebiological studies with cencenergetic neatrens. Radiat. Res.

54, 431-443 (1973).

11.

H.T. Sicia, R. LeGo, G. Cucater, J. Cacher and M. Scurguignon,

For=ation de chremesemes dicentriques dans les lymphocytes hu=ains seemis in vitre a un flux de rayonnement mixta (gama, neutrens).

In Advances in Phvsical and 3feTocical Radiatien Cetectors (IAEA),

pp. 633-645. Intarnaticnal Atomic Energy Agency, Vienna,1971.

12.

A.A. Awa, Chremosc e abarrattens in scratic cells. y. Radiat kes.

16 Suppl.,122-131 (1975),

13.

T. Ishima 2, T. Heshinc, M. Ichimaru, H. Okada, T. Temiyasu, T.

Tsuchfecto and T. Yamacccc, Leukemia in atemic beca sur/ivers, Hiroshima and Nagasaki, 1 Oct. 1950 - 20 Sept. 1966. Radiat. Res.

~

45, 216-233 (1971).

14. National Academy of Sciences, National Research Cconcil, Re;cet of the Adviscry Cc=ittee en the Siciegical 5ffects of Icnizing Radiatiens (BE'R Repert),1972.

15.

-H.H. Rossi and A.M. Xailerer, The validity of risk esticatas cf leukemia incidence based an Japanese daca. Radiat. Res. 53, 131-140 (1974).

16.

T.O. Jcces, Radiation insult to the active bene =ar cw as predicted by a methed of CMCRCS, Cak Ridge National'Laboratcry Repor* CR.*tL-TM-5337, 1976.

17.

H.H. Rossi and C.W. Mays, Leukemia risk frca neutrens. Manusc-ipt submi tted fer publication.

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