OFFICIAL ORGAN OF THE RADIATION RESEARCH SOCIETY

RADIATION RESEARCH

MANAGING EDITOR: ODDVAR F. NYGAARD

Volume 51, 1972

Academic Press • New York and London

Copyright © , 1972, by ACADEMIC PRESS, INC.

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RADIATION RESEARCH

OFFICIAL ORGAN OF THE RADIATION RESEARCH SOCIETY

BOARD OF EDITORS: Managing Editor:

G . E . A D A M S , M t . Vernon Hospital, England

M . J . B E R G E R , National Bureau of Standards

J . G . C A R L S O N , University of Ten-nessee

R. A . C O N A R D , Brookhaven National Laboratory

C. C. C O N G D O X , Oak Ridge National Laboratory

S. B . C U R T I S , University of California E . R. E P P , Sloan-Kettering Institute

for Cancer Research T. M . F L I E D X E R , Universität Ulm, Ger-

many J . A . G H O R M L E Y , Oak Ridge National

Laboratory M . L . G R I E M , University of Chicago

O D D V A R F. N Y G A A R D , Department of Radiology, Case Western Reserve University, Cleveland, Ohio 44106.

R. H . H A Y N E S , York University, Cahada

J . J A G G E R , University of Texas R. H . J O H N S E N , Florida State Uni -

versity R. F . K A L L M A N , Stanford University P . R I E S Z , National Institutes of Health W . C . S N I P E S , Pennsylvania State

University H . D . S U I T , University of Texas J . K . T H O M A S , University of Notre

Dame J . F . T H O M P S O N , Argonne National

Laboratory L . J . T O L M A C H , Washington University G . M . W O O D W E L L , Brookhaven Na-

tional Laboratory

OFFICERS OF THE SOCIETY: President, A . D . C O N G E R , Temple University, Philadelphia,. Pennsylvania.

Vice President (and President Elect)/*V. IP. B O N D , Brookhaven National Laboratory, Upton, Loflg IsIahHf*« " £

Secretary-Treasurer, M A X ^T^LhE^Depi. Rad. and Rad. Biol . , Colorado State University, Ft . Collins, Colorado 80521

Managing Editor, O D D V A R F. N Y G A A R D , Case Western Reserve LTniversity, Cleveland, Ohio

E x e c u t i v e S e c r e t a r y . R I C H A R D J . B U R K , J R . , 4211 39th Street, N . W. , Washington, D . C . 20016

Assistant t o M a n a g i n g Editor: D O R O T H Y D . S C H O T T E L I U S , University of Iowa, Iowa Crty, Iowa

ANNUAL MEETINGS: 1973: Apr i l 29-May 3, St. Louis, Missouri 1974: July 13-20, V International Congress Radiation Research, Seattle,

Washington

VOLUME 51, 1972

Copyright © 1972, by Academic Press, Inc., New York, N. Y. 10003, U. S. A. Second class postage paid at Baltimore, Md. 21202

Councilors Radiation Research Society 1971-1972

P H Y S I C S

R. J . Shalek, University of Texas S. B . Curtis, University of California

B I O L O G Y

R. F . Kallman, Stanford University G. W . Casarett, University of Rochester

M E D I C I N E

H . Spencer, V . A . Hospital, Hines, Illinois C. C . Lushbaugh, Oak Ridge Associated Universities

C H E M I S T R Y

Jack Schubert, University of Pittsburgh W . M . Garrison, University of California

A T - L A R G E

E . L . Alpen, Battelle Memorial Institute G. F . Whitmore, Ontario Cancer Institute

RADIATION RHSEARCH 51, Üi-V (1972)

CONTENTS OF VOLUME 51

N UM HER 1, JULY 1972

U . N. KULKARNI , V. SUNDARVRAMAN, AND M. A . PRASAD. The J)ose Across a Plane Bone-Tissue Interface 1

HAROLD C. B O X , WILLIAM 11. POTTHR, AND EDWIN E. BUDZINSKI. Radical Ion Saturation in Some Sulfur Compounds X-Irradiated at 4.2°K 10

A L A N 11. CHIPPHRFIELD AND DAVID M. TAYLOR. The Binding of Thorium (IV), Plutonium (IV), Americium (III) and Curium (III) to the Constituents of Bovine Cortical Bone I n V i t r o 15

GUNNAR SAXEB0L, THOR B. MKL0, AND THORMOD HHNRIKSEN. Electron Spin Resonance Studies and INIX) MO-Calculations of Electron Irradiated Peptides. A Single Crystal of N-Acetylglycine 31

S. N. BHATTACHARYYA AND K . P. K U N D U . On the Radiolysis of Aqueous Solutions of Nickel (II) Ethylenediamine Tetraacetate 45

DONALD J . F L U K E . Temperature Dependence of the Direct Action of Ionizing Radiation on Beef Heart Lactate Dehydrogenase: Enzyme Activity, Substrate and Coenzyme Affini ties 56

II. H E I T , T. M. FLIKDNK-R, AND I. FACHE. Bone Marrow Regeneration in Germfree NO-2 Mice After 700 Rad Whole Body Irradiation 72

JERROLD M. WARD AND JAMES F. WRIGHT. Pathology of Radiostrontium Exposure in Cats 84

1). A. AGNEW AND L. 1). SKARSGARD. Sensitization of Anoxic Mammalian Cells to Radia-tion by Triacetoneamine-N-Oxyl. Effect of Pre- and Postirradiation Treatment 97

STEPHEN M. FEINGOLD AND ERIC W. H A H N . Postconception Development of Rat Ova Follovving X-ray Induced Superovulation 110

WILLIAM A. CRAMP AND M A Y A E L G A T . The Effects of Ionizing Radiation on Thymidine Uptake into Escherichia coli B / r and Bs-i 121

BEATRIZ MAZAR BARNETT. Radioprotective Effects of Dimethyl Sulfoxide in Drosophila melanogaster 134

S. K. Ho AND Y. L. H O . The Modification of the Yields of Single Strand Breaks in DNA of Gamma-Irradiated Escherichia coli 142

T O R E SANNER AND ALEXANDER PIHL. Effects of X-Rays on the Regultory Functions of Glutamate Dehydrogenase from Beef Liver 155

CHRISTOPH ER S. POTTEN. Some Observations on Melanin Synthesis Anomalies in Mouse Hair Follicles After Treatment with X-Rays or Actinomycin D 167

HERTA SPENCER, JOSEPH SAMACHSON, EDWARD P. HARDY JH. , AND JOSEPH RIVERA. JofTect

of Orally and Intravenously Administered Stable Strontium on 90Sr Metabolism in Man 190

Obituary for Henry Alexander Blair 204 Obituary for Antoine Lacassagne 206 BOOK REVIEW 209

Copyright © 1972 by Academic Press, Inc. All rights of reproduction in any form reservcd.

NUMBER 2, AUGUST 1972

HERBERT WEISS, EDWARD R . EPP, AND J A N E HKSLIN. The Energy Spectrum of Electrons in Water Irradiated with 10- to 20-MeV Electron Beams 211

W . H . ELLKTT AND L. A . BRABY. The Microdosimetry of 250 kVp and 65 kVp X Rays, 6 0 Gamma Rays, and Tritium Beta Particles 229

ANTHONY W . FORD-HUTCHINSON AND DERYCK J . PERKINS. 46Scandium Metabolism; Binding to Metalloproteins i n V i v o and i n V i t r o 244

WELDON G . BROWN AND EDWIN J . HART. The Oxygen Atom: A Primary Species in Irradiated Water 249

K . R . LYNN. Anomalous Behavior Düring y-Irradiation of Chymotrypsin and Trypsin under Nitrous Oxide 254

K . R . LYNN. Effects of y-Irradiation on a Silica-Trypsin Compound Suspended in Aqueous BufTer 265

C . J . G i L L E S P i E , G . S. GISLASON, D . L . D U G L E , AND J . 1). CHAPMAN. Random Break Analyxis of DNA Sedimentation Profiles 272

ZBIGNIKW OLKOWSKI. Radioautographic Studies on the [3H]Uridine Incorporation into the Motor Neurons of the Spinal Cord of X-Irradiated Mice 280

T . R . HOPKINS AND JOHN D . SPIKES. Conformational Changes in Ribonuclease Düring Photodynamic Inactivation 293

EXACUSTODIAN PAUSESCU, TRAIAN TEODOSIU, AND RODICA CHIRVASIE. Effects of Total Exposure to 6 0Co y-Radiation on Cerebral Nicotinamide Nucleotides and Glutathione in Dogs 302

M . R . R A J U , M . GNANAPURANI, B . STACKLER, U . MADHVANATH, J . HOWARD, J . T . LYMAN, T . R . MANNEY, AND C . A . TOBIAS. InfVuence of Linear Energy Transfer on the Radioresistance of Büdding Haploid Yeast Cells 310

A . D E C L E V E , G . B. GERBER, A . LEONARD, M . LAMBIET-COLLIER. A . SASSEN, AND J . R. MAISIN. Regeneration of Thymus, Spleen and Bone Marrow in X-Irradiated AKR Mice 318

T . E . FRITZ, W. P. NORRIS, J . A . TAYLOR, AND N . D . K R E T Z . Effect of X-Irradiation on the Thyroid Gland of Beagles Fed a Restricted Iodide Di et 333

G L E N N N . TAYLOR, T . F. DOUGHERTY, C . W. M A Y S , R . D . LLOYD, 1). R . ATHERTON, AND W. S. S. J E E . Radium-Induced Eye Melanomas in Dogs 301

JOHN S. KREBS AND DAVID C . L. JONES. The LDäo and the Survival of Bone-Marrow Colony-Forming Cells in Mice: Effect of Rate of Exposure to Ionizing Radiation 374

J . L. BATEMAN, H. H . ROSSI, A. M . K E L L E R E R , C . V. ROBINSON, AND V. P. BOND. Dose-Dependence of Fast Neutron RBE for Lens Opacification in Mice 381

K . L. JACKSON AND G . M . CHRISTENSEN. Irreparable Interphase Injury Produced by X-Irradiation of the Rat Thymus i n V i v o 391

HOWARD B. NHWCOMBE AND JOHN F . MCGREGOR. Increased Embryo Production Follow-ing Low Doses of Radiation to Trout Spermatozoa 402

VIMALA R. DEVI AND EDMUND GUTTES. Macromolecular Syntheses and Mitosis in uv-Irradiated Plasmodia of Physarum Polycephalum 410

Abstracts of Papers for the Twentieth Annual Meeting of the Radiation Research Society, Portland, Oregon May 14-18, 1972 431

NUMBER 3, SEPTEMBER 1972

U. OLDENBURG AND J . BOOZ. Calculation and Measurement of Neutron-Produced Single-Event Spectra 551

L. A. BRABY AND W. H . E L L E T T . Ionization in Solid- and Grid-Walled Detectors 569 P. CEVC AND M. SCHARA. Electron Paramagnetic Resonance Study of Irradiated Tooth

Enamel 581

J . A. KNIGHT. Radiolysis of Aniline 590 B. C . WARD, J . R. CHILDRESS, G. L. JESSUP, JR. , AND W . L. LAPPENHUSCH. Radiation

Mortality in the Chinese Hamster, Cricetulus griseus, in Relation to Age 599 J . F. SPALDING, N . J . BASMANN, II. F. ARCHULETA AND O. S. JOHNSON. Comparative

Effects of Dose Protraction by Fractionation and by Continuous Exposure 608 1). K. WATKINS. A Differential Effect of Ionizing Radiation on the Synthesis of Deoxy-

ribonucleic Acid in Ascites Cells in Stationary and Multiplying Phases 615 R. E . BARR AND X . J . MUSACCHIA. Post Irradiation Hibernation and Radiation Response

of Ground Squirrels: Telemetry Surveillance 631 NANCY L. OLEINICK. The Radiation-Sensitivity of Mitosis and the Synthesis of Thymi-

dine Kinase in P h y a a r u m polycephalum: A Comparison to the Sensitivity to Actino-mycin D and Cycloheximide 638

ANTHONY C . JAMES. Dose to Osteogenic Cells from Plutonium-239 Deposited in Rat Bone 654

JOHN R. STRANGE AND R. L. MURPHREE. Exposure-Rate Response in the Prenatally Irradiated Rat: Effects of 100 R on Day 11 of Gestation to the Developing Eye 674

R. GOLDSTEIN AND S. OKADA. Further Studies of Radiation-Induced Interphase Death of Cultured Mammalian Cells 685

SHIGETOSHI ANTOKU. RBE of Pulsed Radiations by Lethality in Mice: Cultured Mam-malian Cells and Bacteria 696

ANNOUNCEMENT 705 JOKRATUM 706 AUTHOR INDEX 707 SUBJECT INDEX 709

RADIATION RKSEARCH 51, 381-390 (1972)

Dose-Dependence of Fast Neutron RBE for Lens Opacification in Mice1

J . L . B A T E M A N , 2 H . H . ROSSI , 8 A . M . K E L L E R E R , 3 C. V . R O B I N S O N , 4

A N D V . P . B O N D 5

Radiological Research Laboratory, Department of Radiology, Columbia University, New York, New York and Brookhaven N a t i o n a l Laboratory, Upton, New York

B A T E M A N , J . L . , R O S S I , H . H . , K E L L E R E R , A . M . , R O B I N S O N , C . V . , A N D B O N D , V . P . Dose-Dependence of Fast Neutron R B E for Lens Opacification in Mice. Radial Res. 51, 3 8 1 - 3 9 0 (1972) .

Opacification of the optic lens in mice has been evaluated after exposure to the following radiations and doses: 2 5 0 k V p x-rays, 4 . 5 - 1 , 0 0 0 rads; 14 M e V neutrons, 0 . 5 - 6 0 rads; 1.8 M e V ncutrons, 1 -36 rads; and 0.43 M e V neutrons, 0 . 0 2 - 1 0 4 rads.

Highly refined techniques of serial i n v i v o lens examination and scoring of minute defects (opacities) were employed for tliis very radiosensitive Sys-tem. Data analysis was based on the relative accumulation of opacities in irradiated compared to untreated lenses. (Both revealed the same degen-erative process.)

A nonparametric analysis of the Observation discloses tliat the R B E is inverscly proportional to the Square root of the neutron dose and that it can reach values in excess of 100 . The findings are in accord with the theory of dual radiation action.

INTRODUCTION

The mammalian optic lens, long of interest for radiation hazard considerations in man, has also served as an assay System of radiobiological value for many investi-

1 This investigation was supported by Contract AT-(ll-l)-3243 for the U.S. Atomic Energy Commission; USPHS, Food and Drug Administration, Bureau of Radiological Health, re-search grant RL 74; and research grant CA 12536 from the National Cancer Institute.

2 Lahey Clinic, Boston, Massachusetts. 3 Radiological Research Laboratory, Department of- Radiology, College of Prrysicians and

Surgeons, Columbia University, New York, New York. 4 Health Sciences Center, State University of New York at Stony Brook, New York. 5 Brookhaven National Laboratory, Upton, Long Island, New York.

381 Copyright © 1972 by Academic Press, Inc. AH rights of reproduction in any form reserved.

382 BATEMAN E T A L .

gators. The inspections for accumulated visibly defective lens fibers, descendant from the relatively hypoxic proliferative lens epithelium are serial and nondestruc-tive. These features combine to create a potent investigative tool, despite limitations due to the necessity to employ an arbitrary, but reproducible, observer-based scoring scale. This difficulty is largely eliminated if the relative biological effective-ness (RBE) is analyzed.

This series of studies was stimulated by the development of a monoenergetic fast neutron technique ( 1 ) which was first employed at this laboratory for the study of early effects in mice 8 ) . The available discrete energies of neutrons provide, along with comparison with x-rays or 6 0 C o gamma rays, a broad selection of radia-tion quality which is of evident value toward the clarification of basic radiation mechanisms.

Some of the experiments described here have been dealt with in part in previous papers (4, 5 ) . Radiation doses of intermediate magnitude were involved, and lens opacification in the anterior axial (epithelial) " A " region and in the posterior sub-capsular (fiber) " V " region were both termed "radio-induced" despite the evidenco of changes wdth age in the controls which were indistinguishable from those appear-ing earlier in the irradiated lens.

The present paper assembles the data from the earlier studies and two more recent studies which employed doses which evoke no detectable effects in most other animal and plant Systems. The low-dose region was of particular interest be-cause the results in the first two lens experiments were compatible with the generally held view that fast-neutron R B E values rise wdth decreasing dose.

The present studies are consistent with ionizing radiation acting by increasing the rate of a natural aging process, rather than by creating an abnormal de n o v o Situation.

MATERIALS AND METHODS

Exposures to x-rays were performed with a 250 kVp G . E . Maxitron therapy unit operating at 30 mA. In the various experiments the H V L ranged from 1.25 to 2.5 mm C u and the dose rate from 17 to 115 rads/minute 6. Uni t density material was employed in thicknesses of several mm for buildup and about 10 cm for backscatter.

Exposures to neutrons of 0.43 and 1.8 M e V were carried out as previously de-scribed (4)-

Exposures to 14 M e V neutrons utilized a Van de Graaff generator to produce the 6 The x-ray dose rates were substantially higher for Expts G and H than for Expt D. The

difference is not considered to be important to the effects discussed in this paper. In a separate study (17) no difference was found between 2 and 100 rads per minute for lens opacification resulting from exposure to 250 kVp x-rays made under hypoxic conditions. The sensitivity (opacification) of the lens in these latter exposures resembled that of previous experiments with exposures made in room air (see below).

L E N S R B E O F F A S T N E U T R O N S 383

3 H(d,n) 4 He reaction. Mice were located on an eight-station circle, with body axes pointed at the target, at a 75° angle to the forward beam axis. The mouse noses were pointed towards the target, with the eyes at 10.3 cm distance from the center of the target. The dose was measured by means of a specially constructed detector which is a phantom in the shape of a mouse containing a small toroidal ionization Chamber in the general location of the eyes. It has been described previously ( 6 ) .

Table I gives the protocols for the four experiments which yielded the data analyzed in this publication. Except for a few double groups each experimental

T A B L E I

PROTOCOLS OF EXPERIMENT

Radialion type and absorled dose i n rads Total number of

v ' x p t 250 kV 14 MeV 1.8 MeV 0.43 MeV exatninations» x-rays neutrons neutrons neutrons

0 (Controls)

M 4.5

12.0 30.0

0.55 1.65 4.83

0.022 0.106 0.531

13

0 (Controls)

6.0 1.0 0.54 12.0 4.5 1.08

H 24.0 14.8 2.08 17 48.0 30.5 4.10

6.05

0 (*Controls)

50* 1.2* 1.1* 150 6.1 5.3 350 18.2 15.9

36.4 31.8

0 (Controls)

70 160 260 400 600

7.2 16.2 27.0 41.3 61.2

104

14

a Each examination involves typically 40 lenses ineach group except for 80 in groups marked by an asterisk (*).

384 B A T E M A N E T A L .

group involved about 24 mice in which at least 40 lenses were scored at each exam-ination. The excess number of animals permitted sustained scoring of 40 lenses despite losses by death of some of the animals.

BNL-Stoner strain (white Swiss) female mice were employed in these investiga-tions. The animals averaged 13 weeks of age at the time of irradiation in some of the experiments; in Expts H and G the average age was six weeks. Supporting studies indicate that radiosensitivity is somewhat increased at an earlier age. Although such a difference would be unacceptable in dose-effect studies, i t should have far less (if any) effect on R B E studies. In fact the higher-dose results obtained in the H and G experiments agree with those of the other experiments.

The mice were maintained on Purina Chow pellets and water ad lib. Temperature and humidity were controlled and there were ten mice to a cage. Serial examinations with a 160 power Bausch & Lomb slit-lamp microscope were begun at four weeks after exposure, with an initial interval of one week between examinations, gradually lengthening to three weeks by one year postirradiation. Mice were examined in the conscious state, after dilation of their pupils by 1 % homatropine. Exposure-group assignment of mice was not known to the observer until all animals had been scored. Mice were held rigidly in a fixture permitting rapid and accurate positioning for examination.

Visible opacities were scored as to size and recorded separately for the anterior " A " and posterior " V " regions of the lens. The former appears to be a hyperplastic lesion which begins with a "pil ing up" of cells in the central portion of the lens epithelium and proceeds to intrusion of a portion of this mass among packed mature lens fibers. Actual opacification begins only after the latter event. Opacities in the " V " region begin as scattered discrete tiny defects, probably occurring in the pos-terior distal portion of lens fibers. It is feit (7, 8 ) that these develop from lens cells derived from abnormal precursor cells resident in the germinal zone of the lens epithelium. " V " opacification becomes evident more quickly postirradiation and progresses at a faster rate than " A " opacification. The data analyzed here were for " V " opacities only.

E F F E C T SCALE AND DATA ANALYSIS

The scale of visual estimate of opacity level has been previously described (4) and, although based on individual judgement, i t has been found to be highly re-producible. It utilizes 15 progressively larger divisions instead of the three or four arithmetically progressive divisions conventionally used to cover the ränge from 0 to 100 % opacity ( 6 , 9, 1 0 ) . The small intervals toward the lower end of this visual scale appear justified on the basis of sensitivity and reproducibility tests.

Two examples of group scores are given in Table II . The groups selected are from Expt M and are controls and subjects exposed to 22 mrad of 0.43 M e V neu-trons. In each group 40 lenses were examined at 13 different times. The latter are

T A B L E II F R KQUKNCIKS OF LKNS OP ACITY SCORKS IN Two Gitoui»}" > OF E XI'KRIM KNT M

Score \

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Age (weeks)

21 40 23 39 1 Controls 25 10 27 30 4 29 35 2 3 31 31 6 2 1 34 29 8 1 1 1 37 11 19 6 1 1 2 41 18 13 5 2 1 1 44 18 14 1 1 2 1 2 1 48 23 9 2 2 1 3 52 12 14 3 9 2 2 1 1 1 1 56 1 20 10 4 2 1 1 1

21 38 2 23 38 2 0.43 MeV neutrons 25 33 5 1 1 0.022 r a d at 27 30 6 1 1 2 18 weeks of age 29 22 11 3 2 1 1 31 22 12 4 1 1 34 17 19 3 1 37 17 16 5 1 1 41 14 20 1 1 3 1 44 13 23 1 1 2 48 3 23 5 3 2 1 2 1 52 3 15 9 5 3 2 1 1 1 56 18 10 1 4 1 4 1 1

25 IG

O

a

o

00 ao

386 B A T E M AN E T A L .

given as the age of the animals in weeks; irradiation having taken place at the age of 18 weeks. Although the examples given in Table II represent a total of more than 1,000 individual eye examinations, they cover only about 5% of the total which was nearly 20,000.

At least two methods of data analysis have been used in previous lens opacifica-tion experiments including score averaging (9-11) and a dichotomized scale-inde-pendent method (#). We have considered other more elaborate procedures of which two (Robinson, in preparation, and Kellerer, in preparation) will be rcported sep-arately. The method of Kellerer is used for the present analysis. The principal fea-ture of this approach is the elimination of the necessity to construct dose-effect curves before the RBE-dose relation is derived. Instead each group of mice exposed to an x-ray dose D x is directly compared to each group of mice exposed to a neutron dose D t l . If the effect of D x is found to be significantly higher than that of D n , the R B E must be less than D x / D n . Conversely, if the effect of D x is found to be sig-nificantly less than that of D n , the R B E must be greater than D x / D n . In this way one excludes certain ranges of R B E values at each neutron dose, and as the result of all comparisons one obtains a confidence region for the RBE-dose relation.

This makes the analysis independent of the a rb i t ra ry choice of the scale of effect. Scale independence is also a requirement for the Statistical test used i n the compar i -son of x-ray and neutron doses. For this reason a parameter free rank-order test, namely the Mann-Whitney test, has been used. A l l the lenses belonging to the two groups which are compared are arranged in a common rank order according to their score at a certain time after irradiation. Application of the Mann-Whitney test to this rank order shows whether the effect level in the two groups is significantly different.

No significant differences in the RBE-dose relations have been found when the observations, at different times after irradiation, were analyzed. But the confidence region is most narrow for the latest observations.

The results of the analysis by this method are shown for each of the three neu-tron energies in Figs. 1-3. These results represent averages ovcr the values ob-tained when the test was applied to the last three observations in each experiment The solid bars indicate ranges of R B E which are excluded according to the outcome of the individual comparisons. Broad solid bars indicate Statistical significance ex-ceeding 99%, light solid bars indicate significance exceeding 95 %. Arrows stand for differences in effect level which are not statistically significant. The curves represent the shape of the dose-RBE dependence as postulated by the theory of dual radiation action {12) and they have been fittcd as explained below. Figure 4 shows all three lines for comparison.

DISCUSSION

It is evident from Fig. 4 that the R B E varies far more with dose than with neu-tron energy. There is at least a 50-fold Variation in the R B E of 0.43 M e V neutrons in the dose ränge investigated. The R B E for neutrons becomes much more than 10

LENS RBE OF FAST NEUTRONS 387

at low doses and at the energy of 0.43 M e V it appears to exceed 100 at 22 mrads. Such R B E values are far iarger than those hitherto rcported for any mammalian system A n obvious reason for the exceptionalty high R B E is that it was possible in our study to accuratefy assess the effects of doses that are exceptionally low.

Since among all the radiations employed in these studies 0.43 M e V neutrons are

NEUTRON DOSE / RAD

FIG. 1. RBE of 0.43 MeV neutrons relative to x-rays for the induction of lens opacification in the mouse as a function of neutron dose.

The solid bars indicate the ranges of RBE values which, according to the comparison of x-ray and neutron doses are excluded. ßroad bars: significance exceeding 99%; light bars: significance exceeding 95%; arrows: nonsignificant differences. The solid line corresponds to a formula given by Kellerer and Rossi (1971).

NEUTRON DOSE / RAD FIG. 2. RBE of 1.8 MeV neutrons relative to x-rays for the induction of lens opacification

in the mouse as a function of neutron dose. The representation is analogous to that in Fig. 1.

388 B A T E M AN E T A L .

10-V

RBE

10

.01 I 10 NEUTRON DOSE/ RAD

FIG. 3. RBE of 14 MeV neutrons relative to x-rays for the induction of lens opacification in the mouse as a function of neutron dose. The representation is analogous to that in Fig. 1.

10-

iO2

RBE

10 r-

I .01 .1 10 10* 10-

NEUTRON DOSE / RAD

FIG. 4. Comparison of the three dose-RBE relations in Figs. 1-3.

the most potent, they were the subject of especial attention. Their effects were studied over an unusually (and perhaps uniquely) wide 5000-fold Variation of dose. It should be noted that at the lowest dose (22 mrad) opacification was found to be greater than in controls with a significance that exceeds 99.9% (sce Table II).

The dependence of R B E on dose is the point of departure of the theory of dual-radiation action {12). In fact the early development of the theory was in part moti-vated by the discovery that a portion of the linear section of the curve in Fig. 1 has a slope of — { 1 3 ) . According to this theory, elementary lesions responsible for a variety of effects on higher organisms are produced with a yield, e, that is proportional to the Square of specific energy, z, {14) in regions having a diameter of the order of 1 jum. A n equivalent formulation is given by:

€ ( D ) = k { z D D + D 2 ) (1)

LENS RBE OF FAST NEUTRONS 389

where A: is a constant, zD the dose average of increments of specific energy ( 1 5 ) and D the absorbed dose. Using the subscripts n and x to denote the neutron and x-ray quantities, setting the R B E equal to D x / D n for equal e and assuming equal fc, one obtains

R B E = 2 ( z D , n + D n ) * D , * + V f D t X + 4(f D ,„ + Dn)Dn

For large and small values of D n this expression tends to 1 and (zDttl/zDi3) respec-tively. In the intermediate ränge of doses the R B E is proportional to \ / l / D n if z D , n » ZD,X • In this ränge the log R B E vs log D n curve should have a slope of — }4.

Although the data in Figs. 1-3 indicate a slope of — }4, i t appears that at very high doses the R B E of 0.43 M e V neutrons is likely to be larger than 1. There are also signs of a disagreement at very low doses. For a wide ränge of site diameters, Z D , n / z D t x for 0.43 M e V neutrons is about 55 ( 1 2 ) . A dose-independent R B E near this value has in fact been observed at very low effect levels in somatic mutations of T r a c l e s c a n t i a ( 1 6 ) , but the data in Fig . 1 indicate that the R B E for lens opacifi-cation exceeds this value at the lowest doses investigated. If it is assumed that the experi mental Undings differ from theory only by a constant factor, one may obtain the fit illustrated in Fig . 1 by multiplication of the right-hand side of E q . (2) by 4 and choosing the value of 150 rad for zD>n . The corresponding quantity zDtX for x-rays must be less than 5 rad. Sufficient fit of the data is achieved if zDtX is ne-glected, and in this case E q . (2) reduces to:

R B E = 4 V i + (150/D») (3)

where the neutron dose D n is measured in radialis. As can be seen from Fig. 1 there is very little latitude in the choice of the twro numerical quantities involved. For the other neutron energies the results are subject to considerable Statistical uncer-tainty and the numerical relations are therefore not given.

There may be a connection between the need for a vertical sliift of the theoretical curve and the finding that the murine lens is anoxic ( 1 7 ) . No other dctailed attempt has been made to apply the theory to anoxic Systems, and it is possible that the constant k in E q . (1) is not equal for x-rays and neutrons in this environmental, condition or that some other modification is required. It may well be that oxygena-tion influences the effectiveness of radiation, depending on energy concentrations over distances far smaller than the micrometer scale which seems to be the relevant one in R B E effects. The answers to these questions must await the completion of further research.

ACKNOWLEDGMENTS

The authors are grateful for the capable assistance of Mary R. Snead and Robert A. Brown in obtaining and compiling the lens opacity data. Dr. David Alburger and Robert Lindgren very effectively operated the Van de Graaff generator for the fast neutron exposures.

R E C E I V E D : F e b r u a r 28, 1972

3 9 0 BATEMAN E T A h .

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