SIXTHlSYMPOSIUM ON MICRODOSIMETRY

Brussels, Belgium, May 22-26, 1978

Commission of the European Communities Directorate-General for Research, Science and Education

Biology, Radiation Protection and Medical Research

Edited by J, Booz and H. G. Ebert

Volume II

AEx> B I B L I O T H E K . \

L _

Phys. Tecttn.

Harwood Academic Publishers Ltd. for the Commission of the European Communities

OPENING SESSION

V I I

Chairman : W.K. SINCLAIR

G. SCHUSTER

L.E.FEINENDEGEN

Address of Welcome

B i o l o g i c a l damage from r a d i o a c t i v e n u c l e i incorporated into DNA of c e l l s ; i m p l i c a t i o n s for r a d i a t i o n biology and r a d i a t i o n p r o t e c t i o n ( i n v i t e d paper)

SESSION 1 Chai rman A. WAMBERSIE

J.R.K. SAVAGE

G.W. BARENDSEN

Some thoughts on the nature of chromosomal a b e r r a t i o n s and t h e i r use as a q u a n t i t a t i v e end-point for r a d i o b i o l o g i c a l s t u d i e s ( i n v i t e d paper)

RBE-LET r e l a t i o n s for induction of reproductive death and chromosome a b e r r a t i o n s in mammalian c e l l s

SESSION 2 Chairman : J.A. DENNIS

V.P. BOND

D.E. CHARLTON J. BOOZ J. FIDORRA Th. SMIT L.E. FEINENDEGEN

G. TISLJAR-LENTULIS P. HENNEBERG Th. MIELKE L.E. FEINENDEGEN

RBE of Η beta rays and other low-LET r a d i a t i o n s at low doses and/or dose r a t e s ( i n v i t e d paper)

Microdosimetry of r a d i o a c t i v e n u c l e i incorporated into the DNA of mammalian c e l l s

125 DNA strand breaks induced by I in cultured human kidney c e l l s and t h e i r r e p a i r

SESSION 3 Chairman : N. PARMENTIER

D. FRANKENBERG Μ. FRANKENBERG-SCHWAGER W. GRUNDLER E. H. KRÜGER H.G. PARETZKE W. POHLIT G. RIMPL

B. FERTIL P. DESCHAVANNE B. LACHET Ε.P. MALAISE

Radiation s t u d i e s at the p h y s i c a l , molecular, c e l l u l a r and macrocolony l e v e l

S u r v i v a l curves of n e o p l a s t i c and non transformed human c e l l l i n e s : s t a t i s t i c a l a n a l y s i s using d i f f e r e n t models

SESSION 4 Chairman : S. WAGNER

J.L. MAGEE A. CHATTERJEE

M. TERRISSOL J.P. PATAU T. EUDALDO

Theory of e l e c t r o n t r a c k s with e x p l i c i t c o n s i d e r a t i o n of track-end e f f e c t s

A p p l i c a t i o n ä la microdosimetrie et ä la ra d i o b i o l o g i e de la simulation du transp o r t des o l e c t r o n s de basse energie dans l'eau ä l ' e t a t l i q u i d e

SESSION 4 ( c o n t . )

V I I I

R.N. HAMM H.A. WRIGHT J.E. TURNER R.H. RITCHIE

S p a t i a l c o r r e l a t i o n of energy dep o s i t i o n events in i r r a d i a t e d l i q u i d water

SESSION 5 Chairman : R.V. RECHENMANN

T. BUDD M. MARSHALL

C S . KWOK M. MARSHALL

B.J. FORSBERG Τ.Ε. BURLIN

R. BLOHM D. HARDER

Low pressure cloud chamber s t u d i e s -I - Methods of a n a l y s i s of i o n i s a t i o n d i s t r i b u t i o n s

Low pressure cloud chamber s t u d i e s -I I - The determination of a high r e s o l u t i o n t i s s u e -equivalent gas for the study of α - p a r t i c l e t r a c k s

R e l a t i o n s of secondary e l e c t r o n emission to microdosimetry and a p p l i c a t i o n s to two-target theory

P h y s i c a l i n t e r a c t i o n s of low-energy e l e c t r o n s i n s i n g l e and twin t a r g e t s

SESSION 6 Chairman : T.E. BURLIN

M.N. VARMA J.W. BAUM P. KLIAUGA

W.E. WILSON L.H. TOBUREN H.G. PARETZKE

L.A. BRABY W.C. ROESCH

Microdosimetric r e s u l t s obtained by p r o p o r t i o n a l counter and i o n i z a t i o n chamber methods : a comparison

C a l c u l a t i o n of energy deposition spectra in small gaseous s i t e s and i t s a p p l i c a b i l i t y to condensed phase

Direct measurements of f ( z ) for f a s t e l e c t r o n s

B. FORSBERG Μ. JENSEN L. LINDBORG G. SAMUELSON

Determinations of the dose mean of s p e c i f i c energy for conventional X-rays by variance-measurements

SESSION 7 Chairman : M. TERRISSOL

POSTER SESSION I : P a r t i c l e track s t r u c t u r e and slowing down

A. CHAMBAUDET Ph. ROMARY H. ROULET A. BERNAS

Diametre des t r a c e s r£velees dans quelques detec t e u r s polym£riques et parcours " e f f i c a c e " des rayons ό'

A. CHATTERJEE J.L. MAGEE

Rel a t i o n s h i p of the tr a c k s t r u c t u r e of heavy p a r t i c l e to the p h y s i c a l d i s t r i b u t i o n and chemical e f f e c t s of r a d i c a l s

D. COMBECHER J . KOLLERBAUR G. LEUTHOLD H. G. PARETZKE G. BURGER

Energy spectra of degraded e l e c t r o n s in water vapour and in carbon

B. GROSSWENDT E. WAIBEL

Determination of b a c k s c a t t e r i n g c o e f f i c i e n t s for low energy e l e c t r o n s in d i f f e r e n t gases

SESSION 7 (cont.)

I X

G.S. HURST S.O. KRAMER C.E. BEMIS, J r . J.P. YOUNG

Detection of s i n g l e atoms in p a r t i c l e t r a c k s

A. JANSSENS G. EGGERMONT R. JACOBS

Experimental study of the c a v i t y theory, using a high pressure i o n i z a t i o n chamber

R.H. RITCHIE R.N. HAMM J.Ε. TURNER H.A. WRIGHT

The i n t e r a c t i o n of swift e l e c t r o n s with l i q u i d water

M. SCHNEIDER J. BÖHM Κ. HOHL FELD Η. REICH

Eine Apparatur zur Messung des V e r l a u f s der Ionendosis an Grenzschichten

B. SENGER E. WITTENDORP R.V. RECHENMANN

<5-ray production along medium energy α p a r t i c l e s c r o s s i n g t i s s u e - l i k e media

J.E. TURNER R.N. HAMM H.A. WRIGHT R.H. RITCHIE R. KATZ

Ca l c u l a t e d e l e c t r o n slowing-down spectra for l i q u i d water i r r a d i a t e d by X and gamma rays - I m p l i c a t i o n s for photon RBE

E. WITTENDORP Β. SENGER J.B. SANDERS R.V. RECHENMANN

Heavy secondaries e j e c t e d by primary medium energy α p a r t i c l e s c r o s s i n g dense t i s s u e - l i k e media

R. KATZ Report on poster Session I

SESSION 8 Chairman : E. HALL

A.M. KELLERER Radiation c a r c i n o g e n e s i s at low doses ( i n v i t e d paper)

R. KATZ High LET c o n s t r a i n t s on low LET s u r v i v a l

SESSION 9 Chairman : R. GRILLMAIER

POSTER SESSION I I : A p p l i c a t i o n of microdosimetry to r a d i a t i o n therapy

H.I. AMOLS J.F. DICELLO M. ZAIDER

The RBE at various p o s i t i o n s in and near a large negative pion beam

L.S. AUGUST R.B. THEUS P. SHAPIRO

Gamma measurements with a non-hydrogenous Rossi counter in a mixed f i e l d

G. BURGER E. MAI ER A. MORHART

Radiation q u a l i t y and i t s relevancy in neutron radiotherapy

SESSION 9 (cont.)

J.F. DICELLO M. ZAIDER

I n v e s t i g a t i o n of the microdosimetric c h a r a c t e r i s t i c s of broad, t h e r a p e u t i c beams of negative pions at LAMPF

J. FIDORRA J. BOOZ

The Local d i s t r i b u t i o n of r a d i a t i o n q u a l i t y of a collimated f a s t neutron beam from 15 MeV deuterons on B e r y l l i u m

R.M. HENKELMAN G.K.Y. LAM

Pr e d i c t i o n of b i o l o g i c a l e f f e c t of pion i r r a d i a t i o n using the s t a r d i s t r i b u t i o n to determine the high LET dose

B. HOGEWEG J. ZOETELIEF J . J . BROERSE

R.b.e. for c e l l s u r v i v a l at d i f f e r e n t p o s i t i o n s in co l l i m a t e d neutron beams in r e l a t i o n to d i f f e r e n c e s in l i n e a l energy sp e c t r a

M.A. KENAWY A.M. SAYEO

Neutron absorbed dose measurements in phantom from 252 ,

cf source

J.B. LEROUX Y. HERBAUT J. ROUILLON Jw GIROUX

Spectres de depots d'energie pour l e s rayonnements de f a i b l e TLE - d i s c r i m i n a t i o n neutron gamma dans un champ mixte η - γ

Μ. MAKAREWICZ S. PSZONA

The c a l c u l a t e d mean energy de p o s i t i o n pattern in an ion chamber for neutrons

H.G. MENZEL Η. SCHUHMACHER Η. BLATTMANN

Experimental microdosimetry at high-LET r a d i a t i o n therapy beams

J.P. PATAU C.E. VERNES Μ. TERRISSOL Μ. MALBERT

C a l c u l des c a r a c t e r i s t i q u e s q u a l i t a t i v e s (TEL, F.Q., equivalent de dose) d'un f a i s c e a u de photons de fre i n a g e ä usage m e d i c a l , par simulation de sa c r e a t i o n et de son tr a n s p o r t

A.G. PERRIS O.R. PERRY *F.A. SMITH

LET i n dose d i s t r i b u t i o n s , from s p e c t r a l measurements of charged p a r t i c l e s emitted at the capture of negative pions in b i o l o g i c a l l y s i g n i f i c a n t m a t e r i a l s

G. PFISTER P. STILLER G. HEHN

R e c o i l s p e c t r a in neutron i r r a d i a t e d t i s s u e s and TE-materiaIs

J. ZOETELIEF B. HOGEWEG J . J . BROERSE

Radiation q u a l i t y and absorbed dose at d i f f e r e n t p o s i t i o n s in the primary beam and around the s h i e l d i n g of a neutron generator

J . J . BROERSE Report on poster Session I I

SESSION 10 Chairman : A. ALLISY ( j o i n t l y organized by ICRU and EURATOM)

M.J. BERGER Planned compilation of stopping power and range data

H.H. ANDERSEN Higher-order Z^ c o r r e c t i o n s to the Bethe stopping-power formula

J.A. DENNIS The dependence of stopping-power on p h y s i c a l and D. POWERS chemical s t a t e s

SESSION 10 (cont.) X I

Μ. INOKUTI J.E. TURNER

Mean e x c i t a t i o n energies for stopping-power as derived from o s c i L L a t o r - s t r e n g t h d i s t r i b u t i o n s 675

SESSION 11

POSTER SESSION I I I :

J . CASANOVAS R. 6R0B 6. BRUNET R. SABATTIER J.P. GUELFUCCI D. BLANC

Chairman : M.J. BERGER

Stopping power and r e l a t e d s u b j e c t s

Determination du p o t e n t i e l d ' i o n i s a t i o n de c e r t a i n s hydrocarbures en phase Liquide 689

J . J . COYNE L.J. GOODMAN

p. GOUARD M. CHEMTOB V.D. NGUYEN N. PARMENTIER

A.K.M.M. HAQUE M.J. GEARY

R.B.J. PALMER A. AKHAVAN-REZAYAT

H.G. PARETZKE M.J. BERGER

B.G.R. SMITH J. BOOZ

D.I. THWAITES D.E. WATT

T.K. YEUNG D.E. WATT

D.E. WATT

W , computed from recent nucLear data and W measurements

Une approche p o s s i b l e de l'etude du ralentissement des p a r t i c u l e s chargees Lourdes

The stopping power and s t r a g g l i n g for alpha p a r t i c l e s i n l i q u i d s

Range-energy r e l a t i o n s and stopping power of water, water vapour and t i s s u e equivalent l i q u i d for α p a r t i c l e s over the energy range 0.5 to 8 MeV

Stopping power and energy degradation for e l e c t r o n s in water vapor

Experimental r e s u l t s on W-values and t r a n s m i s s i o n of low energy e l e c t r o n s in gases

Phase e f f e c t s in stopping power for Low-energy heavy charged p a r t i c l e s

M u l t i p l e s c a t t e r i n g c o r r e c t i o n s to measurements of stopping power for slow ions

Report on poster Session I I I

699

707

725

739

749

759

777

793

813

SESSION 12 Chairman W. POHLIT

D.T. G00DHEAD J. THACKER R. COX

P.D. HOLT

The c o n f l i c t between the b i o l o g i c a l e f f e c t s of u l t r a s o f t X-rays and microdosimetric measurements and a p p l i c a t i o n 829

Micro-dosimetry and nano-dosimetry 845

D. CHMELEVSKY A.M. KELLERER H.H. ROSSI

Concepts and q u a n t i t i e s r e l e v a n t to the e v a l u a t i o n of charged p a r t i c l e t r a c k s 855

SESSION 13

X I I Chairman : H.H. ROSSI

R.P. VIRSIK D. HARDER

Chromosome a b e r r a t i o n s in human Lymphocytes induced by photon and eLectron r a d i a t i o n s , and the su b l e s i o n i n t e r a c t i o n modeL

C R . GEARD

A. WAMBERSIE J. VAN DAM G. LAUBLIN

Microdosimetry and chromosomal a b e r r a t i o n s f o r monoenergetic neutrons

RBE as a function of depth in a 650 MeV H e + +

beam determined for growth delay i n v i c i a faba and for induction of chromosome a b e r r a t i o n s in a l l i u m cepa

SESSION 14 Chairman : G.E. ADAMS

E.M. FIELDEN 0. SAPORA P.S. L0VER0CK

S. APELGOT J.P. ADLOFF

The r e l a t i o n between s u r v i v a l and the i n i t i a l y i e l d of DNA strand breaks for Ε c o l i B/r

Transmutation e f f e c t s of 3 2 P and "̂*P i n c o r p o r a t e d in DNA

H.G. PARETZKE

H.H. ROSSI R. BIRD R.D. COLVETT A.M. KELLERER N. ROHRIG Y-M.P. LAM

On l i m i t a t i o n s of c l a s s i c a l microdosimetry and advantages of t r a c k s t r u c t u r e a n a l y s i s for r a d i a t i o n biology

The molecular ion experiment

SESSION 15

POSTER SESSION IV:

H.M.A. AL-SHAI8ANI D.E. WATT

M. COPPOLA M. MARTINELLI L. T0MMASIN0

Chairman : D. HARDER

I n t e r p r e t a t i o n of b i o l o g i c a l data

P h y s i c a l processes in the i n a c t i v a t i o n of enzymes by slow heavy ions

C e l l s u r v i v a l and r a d i a t i o n q u a l i t y

R. FACIUS H. BUCKER G. REITZ M. SCHÄFER

Radial dependence of b i o l o g i c a l response of spores of B a c i l l u s s u b t i l i s around t r a c k s of heavy ions

R.E. GRILLMAIER L. BIHY H.G. MENZEL Η. SCHUHMACHER

Chromosome a b e r r a t i o n s t u d i e s and microdosimetry with r a d i a t i o n s of varying q u a l i t y

R. KATZ E.C PENNINGTON

Ra d i o b i o l o g i c a l aspects of s u p r a l i n e a r photographic emulsions

H.P. LEENHOUTS K.H. CHADWICK M.J. SIJSMA

The i n f l u e n c e of r a d i a t i o n s t i m u l a t e d r e p a i r processes on the shape of d o s e - e f f e c t curves

X I I I

SESSION 15 ( c o n t . )

J.W. PURDIE E.R. INHABER N.V. KLASSEN

R.A. ROTH R. KATZ

Μ. SCHÄFER H. BÜCKER R. FACIUS G. HORNECK G. REITZ G. KRAFT

F. SCHOPFER J. KIEFER E. SCHNEIDER G. KRAFT

A. TALLENTIRE D.J.W. BARBER

K.J. WEBER J. KIEFER

J . KIEFER

I n c r e a s e d s e n s i t i v i t y of anoxic mammalian c e l l s i r r a d i a t e d with s i n g l e p u l s e s at very high dose r a t e s

Heavy ion beam model for radiobiology

High L E T - i r r a d i a t i o n of B a c i l l u s s u b t i l i s spores

The i n a c t i v a t i o n of c e l l s by a c c e l e r a t e d heavy ions of very high LET

The i n t e r r e l a t i o n s h i p between pulse length and dose- r a t e w i t h i n the pulse in the enhancement of anoxic damage in wet B a c i l l u s megaterium spores i r r a d i a t e d with p u l s e s of e l e c t r o n s

I n t r a c e l l u l a r measurement of the i n a c t i v a t i o n of ribosomal RNA genes in d i p l o i d yeast c e l l s a f t e r exposure to 6CJCo~Y^rays, 85 kV X-rays and 241-Americiurn-ct - p a r t i c les

Report on poster Session IV

SESSION 16 Chairman : A.M. KELLERER

H.H. ROSSI

J.A. DENNIS

Ra d i a t i o n q u a l i t y and q u a l i t y f a c t o r ( i n v i t e d paper)

Dose l i m i t s and q u a l i t y f a c t o r s : the D e v i l ' s view

SESSION 17 Chairman J . J . BROERSE

C.L. GREENSTOCK R.H. WIEBE

K.H. CHADWICK Η.P. LEENHOUTS

Chemical mechanisms of the i n t e r a c t i o n between r a d i a t i o n and chemical carcinogens

The i m p l i c a t i o n s for r a d i o l o g i c a l p r o t e c t i o n of the s y n e r g i s t i c i n t e r a c t i o n between r a d i a t i o n and other DNA damaging agents

SESSION 18 Chairman : K.H. CHADWICK

J. KIEFER Η. KOCH Κ. KOESTER G. MOCK Ε. SCHNEIDER Κ. WEBER

The molecular and c e l l u l a r b a s i s of the oxygen e f f e c t

SESSION 18 (cont.) X I V

Κ.F. BAVERSTOCK W.G. BURNS R. MAY

The oxygen in the track hypothesis: Microdosimetric i m p l i c a t i o n s

SESSION 19 Chai rman H. DE CHOUDENS

R.S. CASWELL J . J . COYNE

P. KLIAUGA R.D. COLVETT L.J. GOODMAN Y.M. LAM

A.K.M.M. HAQUE S.A. SAQ'AN

Energy d e p o s i t i o n spectra for neutrons based on recent cross s e c t i o n e v a l u a t i o n s

Microdosimetry of 400 MeV/AMU 1 2 C and 450 MeV/AMU ^ A r beams

Microdosimetric study with c y l i n d r i c a l walled and w a l l - l e s s p r o p o r t i o n a l counters

SESSION 20 Chairman : J . BOOZ

C. HERSKIND Κ.Α. JESSEN

W.C ROESCH

J. BOOZ

APPENDIX 1

Measurements i n i n t e r n a l microdosimetry with a w a l l - l e s s p r o p o r t i o n a l counter

I n t e r n a l microdosimetry

Closing of the Symposium

Personal impressions and reviews of d i s c u s s i o n s

G.E. ADAMS

J. BOOZ

J.A. DENNIS

L. LINDBORG

Μ. TERRISSOL

G. TISLJAR-LENTULIS

Some d i s c u s s i o n comments on the mechanisms of s e n s i t i z e r s

Summary of the d i s c u s s i o n s concerning r a d i a t i o n mechanisms of e x t e r n a l r a d i a t i o n s

Impressions of the 6th Microdosimetry Symposium and i t s relevance to r a d i o l o g i c a l p r o t e c t i o n

Summary of d i s c u s s i o n s on e v a l u a t i o n of microdo­simetry data

Summary of the d i s c u s s i o n s concerning e l e c t r o n t r a c k s t r u c t u r e and microdosimetry

Summary of the d i s c u s s i o n s concerning incorporated r a d i o i s o t o p e s

APPENDIX 2 L i s t of p a r t i c i p a n t s

937

THE MOLECULAR ION EXPERIMENT**

H.H. Rossi, R. B i r d , R.D. Colvett, A.M. Ke l l e r e r , N. Rohrig* and Y-M.P. Lam

Radiological Research Laboratory, Columbia University 630 West 168th Street, New York, New York 10032

and

*Medical Department, Brookhaven National Laboratory, Upton, New York

Abstract

In e arly s i m p l i f i c a t i o n s o f the Theory of Dual Radiation Action i t

was assumed t h a t i o n i z i n g r a d i a t i o n s produce lesions which arise from the

combination o f pairs o f sublesions that are produced i n " s i t e s " , i . e .

l i m i t e d regions i n the c e l l nucleus i n which t h i s combination can take

place. In a more r e a l i s t i c treatment, the p r o b a b i l i t y o f combination

depends on the separations at which the sublesions can be produced and

the p r o b a b i l i t y t h a t combination occurs i f such i n i t i a l separations i n t e r ­

vene. The molecular ion experiment i s designed to determine t h i s depen­

dence. Pairs o f ions with varying mean spacing are generated by the

break-up of molecular ions and subsequent divergence by m u l t i p l e coulomb

sc a t t e r i n g i n a f o i l . The emergent ions traverse mammalian c e l l s attached

to the e x i t side o f the f o i l .

The p r i n c i p l e s o f the experimental techniques are discussed and some

i n i t i a l r e s u l t s are presented.

**This i n v e s t i g a t i o n was supported by Grant Numbers CA 15307 and 12536, awarded by the National Cancer I n s t i t u t e , DHEW, and by Contract EP-78-S-02-4733 from the U.S. Department of Energy.

938

Background and objective:

The concepts of microdosimetry were developed because the c e l l s of

higher organisms usually respond to i o n i z i n g r a d i a t i o n i n a non-linear

manner, in that d i f f e r e n t d i s t r i b u t i o n s of absorbed energy r e s u l t i n d i f ­

ferent frequencies of e f f e c t s . The i d e n t i f i c a t i o n of pertinent microdosi-

metric quantities must however be governed by the nature of the dependence

of e f f e c t frequency on energy concentration and by the magnitude of the

domains in which energy concentration i s s i g n i f i c a n t .

The Theory of Dual Radiation Action provides answers to both of these

questions by i t s postulate t h a t r a d i a t i o n i n j u r y i s due to lesions which

i n turn r e s u l t from the p a i r i n g of sublesions that have been produced at

separations that are t y p i c a l l y 1 urn. In an early formulation (1) i t was

stated that ε(ζ), the y i e l d of lesions, i s proportional to the square of

the s p e c i f i c energy, z, or

where Κ i s a constant and ζ i s the value of the s p e c i f i c energy i n s i t e s

( i . e . subnuclear volumes) having a diameter of about 1 ym.

Eq. (1) i s equivalent to

where D is the absorbed dose and ζ the dose mean of the s p e c i f i c energy

produced by individual events i n the s i t e s .

I t was recognized that t h i s formulation can only be an approximation

f o r a number of reasons. These include the necessity of corrections f o r

saturation and f o r v a r i a t i o n of Κ with r a d i a t i o n q u a l i t y . An additional

ε(ζ) = Κ ζ 2 (1)

e(D) = Κ(ζΰ + D 2) (2)

939

s i m p l i f i c a t i o n consists i n the assumed existence of s i t e s i n which there i s

constant p r o b a b i l i t y of i n t e r a c t i o n between sublesions. There i s no cyto-

log i c a l evidence f o r the existence of such volumes and i t seems much more

l i k e l y that sublesions are produced throughout the nucleus and that they

combine with a p r o b a b i l i t y that depends on t h e i r separation. The i n i t i a l

separation of combining sublesions i s then on the average about equal to

the radius of the hypothetical s i t e s .

In a recent generalization (2) of the Theory of Dual Radiation Action

the s i t e concept has been eliminated and the r e l a t i o n given i n Eq. 2 has

been replaced by

c(D) = Κ(ξϋ + D 2) (3)

ξ i s proportional to the integrated product of three functions:

s(x)dx s the expected volume of matrix at a distance χ to χ + dx

from a sublesion. The matrix i s that portion of nuclear material

i n which sublesions can be produced.

g( x ) , the average p r o b a b i l i t y that a pair of sublesions separated

by χ combines to form a lesion.

and t ( x ) d x , the mean energy deposited by the same event at a distance

χ to χ + dx from an energy deposit.

The normalized product

00

*(x) = 9(x) s ( x ) / / g(x) s(x) dx (4)

may be termed the a v a i l a b i l i t y of adjacent l o c i . I f sublesions are produced

randomly i n the matrix, i . e . i f energy i s uniformly imparted to the medium,

<&(x)dx i s the f r a c t i o n of lesions r e s u l t i n g from two sublesions that were

produced at a separation χ to χ + dx. The s i t e radius applicable

940

00

to the s i t e model should be comparable to / χ Φ ( Χ ) dx. ο

Since Φ(Χ) characterizes the dependence of sublesion combination on

separation, i t i s a basic function of radiobiology. The determination of

i t s values f o r i n a c t i v a t i o n of tissue culture c e l l s i s the objective of the

molecular ion experiment.

Basic plan of experiment:

The most d i r e c t determination of Φ(Χ) would be one i n which ra d i a t i o n

i s administered i n pairs of energy deposits of varying separation. However

t h i s does not seem feasible because of the inherent track pattern of energy

deposition.

A less d i r e c t but achievable method consists i n the employment of short

tracks of varying length. Monoenergetic χ rays having energies of the order

of one keV or monoenergetic neutrons of somewhat higher energy could be em­

ployed to determine the value of the inte g r a l given above over various f i n i t e

i n t e r v a l s . Other studies with such radiations have i n f a c t been carried out

(3,4,5). There i s however a major d i f f i c u l t y i n t h a t , as already mentioned,

Κ which depends on the effectiveness with which sublesions are produced i s

very l i k e l y to depend on LET. The nature of t h i s dependence i s largely un­

known but i t may be expected to be especially pronounced near the ends of

tracks.

This d i f f i c u l t y can be avoided i f the i r r a d i a t i o n i s by pairs of paral­

l e l tracks with variable spacing and t h i s i s the modality that has been

adopted. Because of problems of scattering and the minute separations re­

quired, i t was deemed impractical to u t i l i z e collimated p a r t i c l e s , and un­

c o i l ima ted molecular ions are employed instead. Although protons as well

as deuterons are used and the molecules can be triatomic as well as diatomic,

941

the remainder of t h i s discussion w i l l deal with diatomic deuterium molecules.

The ion source of the RARAF Van-de-Graaff accelerator provides an ample

supply of D 2

+ ions which are readily segregated by a magnetic f i e l d . When

these molecules s t r i k e a f o i l , the electron j o i n i n g the deuterons i s s t r i p ­

ped o f f and the two nuclei proceed independently i n tracks that are not

s t r i c t l y r e c t i l i n e a r because of multiple coulomb scatte r i n g . I t can be shown

that f o r any f o i l thickness, a, the separation, s, of the emerging p a r t i c l e s

i s very nearly d i s t r i b u t e d as

f ( s ) = s/B2 · exp(-s 2/ß 2) (5)

where a i s a constant that i s inversely proportional to p a r t i c l e energy,

proportional to the square root of a, and dependent on the material of the

f o i l . Scattering of single p a r t i c l e s was studied to determine β and to

obtain s l i g h t corrections to Eq. 5.

In t h i s i r r a d i a t i o n modality there i s no f i x e d separation of tracks

but a d i s t r i b u t i o n having a width that depends on $. However t h i s poses

no substantial problem since t ( x ) can be calculated f o r e i t h e r condition

following approaches previously outlined ( 6 ) .

The basic experiment consists i n i r r a d i a t i n g c e l l s attached to t h i n

sheets of mylar with deuteron molecules that are incident on the opposite

surface. The survival of c e l l s i s compared with th a t obtained with equal

numbers of single deuterons of the same energy. This condition i s attained

by the simple expedient of introducing a very t h i n scattering f o i l i n t o the

beam pipe at some distance upstream from the c e l l s . There i s n e g l i g i b l e

p r o b a b i l i t y that following break-up by t h i s f o i l , b o t h deuterons pass through

the same c e l l . The r a t i o of survivals f o r uncorrelated and correlated deu­

terons i s studied as a function of f o i l thickness, allowance being made f o r

942

MOLECULAR ION BEAM E X P E R I M E N T

1. Schematic representation of i r r a d i a t i o n by molecular ions. The

molecular ions dissociate e i t h e r in a f o i l contiguous t o the c e l l s

or they are dissociated at some distance upstream from the c e l l s .

The lower sketch i s not t o scale since the thickness of the c e l l s

and the supporting mylar are of the order of a micrometer while

the separation of the breakup f o i l from the f o i l - c e l l combination

is on the order of meters.

BEAM PROFILE MOTOR

(I OF 23)

I 1 10 cm

2. A schematic cross-sectional drawing of the i r r a d i a t i o n f a c i l i t y of

the molecular ion experiment. The major components are i d e n t i f i e d .

9^3

an additional mean separation due to scattering i n the c e l l s which are about

as thick as the thinnest f o i l employed 4 ym). The mean separation at

median c e l l depth has,in experiments carried out thus far,ranged from about

90 to about 250 run.

In these experiments V79 hamster c e l l s are u t i l i z e d and they are syn­

chronized because i t was anticipated that Φ(Χ) might depend on c e l l age.

Technical features:

A series of papers w i l l describe the various d e t a i l s of the molecular

ion research. Although the p r i n c i p l e of the experiments i s r e l a t i v e l y sim­

ple, substantial practical d i f f i c u l t i e s had to be overcome. Here only a few

sa l i e n t features w i l l be mentioned.

The need to i r r a d i a t e the c e l l s i n dishes having a diameter of several

cm results i n a mechanical problem since the t h i n f o i l s are 1iable to rupture

when subjected to a pressure d i f f e r e n t i a l of one atmosphere between the

vacuum chamber and the c e l l environment. I t has thus been found necessary

to expose the c e l l s when they are i n gas at 1/10 atmosphere pressure. This

in turn requires rapid evacuation and careful control of humidity. However

even under the optimum conditions available, i t i s not possible to avoid

the trauma that i s caused by the i r r a d i a t i o n environment together with that

introduced by synchronization with hydroxyurea. In order to reduce the

l i m i t s of error , a considerable number of dishes are i r r a d i a t e d to equal

numbers of associated or random p a r t i c l e s with other dishes serving as con­

t r o l s . ( F i g . 1)

The dishes are placed i n t o a large wheel that rotates at a rate t h a t

i s proportional to the dose rate as measured by a current monitor. The

beam i s delimited by a s l i t and the wheel rotates i n steps of 5 min of arc

944

3. Photograph of the i r r a d i a t i o n f a c i l i t y f o r the molecular ion

experiment. Most of the apparatus surrounding the i r r a d i a t i o n

chamber (large aluminum box) serves to control the c e l l environ­

ment.

945

when ever a predetermined fluence has passed through the s l i t . This ensures

uniformity of i r r a d i a t i o n . Two of the positions on the wheel are occupied

by dosimeters. A l l of the operations including wheel motion, i n s e r t i o n of

the break-up f o i l , dosimetry, etc. are controlled by an on-line computer.

Fig. 2 i s a schematic drawing of the i r r a d i a t i o n chamber and Fig. 3 i s a

photograph showing some of the peripheral equipment as w e l l .

The assay of c e l l survival i s carried out by standard techniques.

I n i t i a l r e s u l t s :

Although a considerable number of i r r a d i a t i o n s have been carried out,

the results obtained to date are f o r only 3 f o i l thicknesses. They are given

p r i m a r i l y to show that the expected e f f e c t does indeed e x i s t . As also a n t i ­

cipated, i t i s more pronounced i n lat e S than at the Gx/S interface pre­

sumably because of differences i n the aggregation of DNA.

Fig. 4 shows the survival r a t i o as a function of absorbed dose f o r c e l l s

i n l a t e S f o r three d i f f e r e n t f o i l thicknesses and Fig. 5 shows the corres­

ponding data f o r G^S. The survival r a t i o i s defined f o r equal doses as

the r a t i o of survival with random p a r t i c l e s and that with associated paVti-

cles. I t i s evident that i n general, with increasing c o r r e l a t i o n ( i . e . with

decreasing f o i l thickness),the effectiveness of deuterons increases, par­

t i c u l a r l y i n l a t e S.

No d e f i n i t i v e attempt has been made to determine Φ(Χ) although the

methods f o r such an analysis are at hand, including adequate formulation of

t ( x ) . However, i t would appear on the basis of i n i t i a l considerations that

Φ(Χ) may turn out to have a complex shape i n which the function decreases

rather rapidly at low χ but much more slowly at large x. V e r i f i c a t i o n of

t h i s impression must await the results of f u r t h e r experiments.

946

1—I ΠΊ Γ late S cells

200 600 800 1000 1200

DOSE (RADS)

Preliminary data on the r e l a t i o n between the survival r a t i o ( r a t i o

of survivals with uncorrelated and correlated ions) as a function

of absorbed dose. The data are f o r c e l l s i n la t e S phase attached

to f o i l of the indicated thicknesses.

2.2

2.0

1.8

1.6

> κ 1.4

0.8

Ί — I — I — Γ

ο 4/im ο 6/Afn Mylar

ι ι ι—Γ G|/S cells

J I I L J I ! L 200 400 600 800 1000 1200

DOSE (RADS)

Preliminary data on the r e l a t i o n between the survival r a t i o ( r a t i o

of survivals with uncorrelated and correlated ions) as a function

of absorbed dose. The data are f o r c e l l s i n G-j/S interface

attached t o f o i l of the indicated thicknesses.

947

Acknowledgements:

William Gross, Leon Goodman, and E.J. Hall made major technical c o n t r i ­

butions to t h i s work and we are grateful f o r t h e i r help.

REFERENCES

1. Kellerer, A.M. and Rossi, H.H. "The theory of dual radi a t i o n action." Current Topics i n Radiation Res. Quart. 8, 85-158 (1972).

2. Kellerer, A.M. and Rossi, H.H. "A generalized formulation of dual radiation action." Radiat. Res. ( i n press).

3. Neary, G.J., Preston, R.Y., and Savage, J.R.K. "Chromosome aber­rations and the theory of RBE. I I I . Evidence from experiments with s o f t X-rays, and a consideration of the effe c t s of hard X-rays." I n t . J. Radiat. B i o l . 12, 317-345 (1967).

4. Cox, R., Thacker, J., and Goodhead, D.T. "I n a c t i v a t i o n and mutation of cultured mammalian c e l l s by aluminum c h a r a c t e r i s t i c u l t r a s o f t X-rays. I I . Dose-responses of Chinese hamster and human d i p l o i d c e l l s to aluminum X-rays and radiations of d i f f e r e n t LET." I n t . J. Radiat. B i o l . 31_, 561-576 (1977).

5. Geard, C.R. and Rossi, H.H. "Microdosimetry and chromosomal aber­rations f o r monoenergetic neutrons." (presented at t h i s symposium).

6. Kellerer, A.M. and Chmelevsky, D. "Concepts of microdosimetry. I I I . Mean values of the microdosimetric d i s t r i b u t i o n s . " Rad. and Environm. Biophys. 12, 321-335 (1975).