Meeting of the Bio-Medical Program Directors

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IU NITED STATES ATOMIC ENERGY CO MEETING OF THE BIO-MEDICAL PROGRAM OAK RIDGE, TENNESSEE OAK FUDGE NATIONAL LABORATORY UNIVERSITY OF TENNESSEE OAK RIDGE INSTITUTE OF NUCLEAR STUDIES Human Studies Project

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ABSTRACTS OF PApEEls REaD AT THIS YI JO AND ABSTRACTS OF PAPERS PRES- BY TITLB OH HiOJECTS U IT HII THE 6000 PROCRAM IN ohl( RIDGE. UT-m AGRICULTUBL RESEBBCH PROGRAM mICAL DI9ISIONs OAK RIDGE INSTITUTE OF NUCLEAR STUDIES

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MEETING OF THE BIOMEDICAL PROGRAM DIRECTORS OAK RlDGE NATIONAL IABORATORY, OAK RID=, TENNESSEE. The Meeting will be held inthe auditorium of the new Research Building, No. 4500, Oak Ridge National Laboratory. portation tothe Oak National Laboratory. issued on board busses. Guests will board busses for transPasses will be 9115 A.M. Presentation of Papers representing Projects o f the Biology Division, Oak Ridge National Laboratory, Carbide & Carbon Chemicals Company, Alexander Hollaender, presiding: 1. Cytogenetic Effects o f Radiation. Richard F. Kimball and 2. Radietion Protection and Enzymology. John R . Totter and Mary Esther Gaulden. Smith, and Norman G. Anderson. L. Pathology and Physiology. Jacob Furth and Arthur C. Upton. 5. Tracer Studies i n Microbial and Plant Metabolism. Stanley F. 6. Biochemistry: Nucleic Acids, Enzymes, and Luminescence. Carson and N. Edward Tolbert. 12$00 Presentation of Papers representing Projects of t h e Health Physics Division, Oak Ridge National Laboratory, Carbide and Carbon Chemicals Company. Karl 2. Morgan, presiding8 8. Interaction of Radiation and Matter. R . D. Birkhoff. 12~50P.M. Adjournment f o r Lunch. Cafeteria, Oak Ridge National Laboratory, OFFICIAL USE ONLY

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OFFICIAL USE ONLY. 10. Radioactive W&ste Disposal Research, Roy J. Morton. 11. Internal Dose Studieso Isabel H. Tipton. 12. The Pattern of Skeletal Deposition of t h e Bone-Seekers. Age and Physiological Behavior of Radiocalcium. S. L. Hansard, Uptake and Retention of trivalent Chromium-Slby the Effects of Whole Body Irradiation of Male Rats upon the Rate of Fetal Mortality in their Offspring. R. L Wuphree. Rake We Le Vis & . a. Lethal Dose and Pathology Studies vrith Large Animals mosed t o High Energy Ion h ing Radiations. John H. Rust, 15. The Clotting Defect i n the Blood of Burros after Irradiation. 4t45 P.M. Busses will be available f o r transportation t o Oak Ridge Tornsit.. 7x00 P.M. Oak Terrace i n Grove Center. Courtesy of t h e Carbide and Carbon Chemicals Coxupany. Oak Ridge Mation81 Laboratory. OFFICIAL USE ONLY

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portation t o the Oak Ridge National Laboratory. 9:15 A.16. Presentation of Papers representing Projects of the Medical Diesion, Oak Ridge Institute of Nuclear Studies. Harshall Brncer, presiding: 16. Radioactive Colloids i n Therapyo Wuld A. Andrum, Lttlcolm Tyor, Ralph Yo Kniseley, and Granvil G. Kyker. 17. Skin Dose from a Cobalt-60 Teletherapy Unit. l0:45 A.M. Business Meeting or' t h e Biomedical Directors. John C. Bugher, M.D.P Director, Division of Biology and Medicine, Washington, 12:30 P.M. Lunch, Cafeteria, Oak Ridge National Laboratory. 1:30 P.M. Tours of Laboratories. Transportation will be available from the Cafeteria t o each of the laboratory areas outside X-10. (1) Health Physics Division, Oak Ridge National Laboratory, X - 1 0 Area, located within walking distance of t h e and Animal Exposure Field. (4) Medical Division, Oak Ridge Institute of Nuclear Studies, Oak Ridge Townsite. Announcements will be mads prior to lunch regarding 8rrangements for transportation t o railroad stations and the Knoxville airport. OFFICIAL USE arm

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(Biology Division, Oak Ridge National Laboratory) Presented by Richard F. Kimball Paramecium - I n agreement with findings an other materials, hypoxia during, but not before or after,X irradiation decreaees the productim of micronuclear mutationa and the inactivation of kam ( a self-reproducing cytoplasmic entity). However, %02 formed outside the cell is not involved, possibly because it cannot diffuse far into the cell. Thus the influence of oxygen must be on locally formed €$02 if it i s on peraxide formation a t a l l In the preeence of few bacteria, X rays exert their main influence on divi - siou delay and nangenetic death by way of peroxide formed outside the c e l l , and hypoxia decreases this effect. Thie result6 both from decreased format i o n and from decreased effectivenese of peraxide under hypaxial conditions. When peroxide cannot accumulate outside the cell^, there is no influence of oxygen upon X-ray-induced division delay and death, euggeeting that too little peroxide is farmed locally i n the cell to produce theee effects. No influence of oxygen tension during irradiation nor of external peroxide ha8 been found on inhibition of pronuclear exchange a t canjugation. Finally, X-ray inactivation of paramecin (an extracellular DNA particle formed by * On leave of abaence -- Fulbright Fellowship

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certain strain8 of Paramecium and capable of killing others) is increaeed by decreased oxygen concentration during irradiation. eulte are moat readily underetood on the view that the relative inrportance of different pathway6 of X-ray action is different for different kinds of biological damage, depending both on the nature and eurr-ings of the material and damage. Bacteriophage -- The proceeaee reeponsible for specific replication of bacteriophage material can be shown t o occur i n a stage of the reproductive cycle during which the vine it eel fie in a noninfective state. A genetic attack seem t o be one of the most hopeful f o r describing the phenomens occurring during this condition. Our attention is focused at this ti no on the phenomenon of genetic recombination with OUT f i r s t objective being t o obtain genetic material which is still far from abundant in this group of organisms. I n addition,the significance of four observaticsns is being cycle of infection and lysis ; (2)drift with tim s in proportion of recom- (1) occurrence of tri parental recombination within a single binants tmrd genetic equilibrium within a single intracellular cycle; i n a cro68 of a disproportionately high number of double recombinante within the same linkage group; (4) occurrence within individual phage particles of local daublings of genetic material. approach t o genetic equilibrium ha6 been measured for different linkage groups. Other experiment8 are directed toward a decision asto whether

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a recombination i n one linkage group tends t o be associated with a recombination in an independent linkage group and whether the negative interference dose, in fact, extend over the entire genetic cmlement. The latter appears t o be the case. All observations may be accounted for by any recombination model which permits repetitive opportunities for exchange of genetic markers within a single intra bacterial cycle. more exactly, we a r e now engaged i n experiments using three llnked genentic In order t o specify such a model markers with which recombination m y be measured simultaneously in two adjacent regions i n euch 8 way that both single and double recombinants may be scored separately. With them markers it is proposed t o measure the negative interference i n individual bacterial cells. Such an experiment should decide whether this phenomenon, ordinarily measured i n the average virus yield from thousands of bacteria, is actually a function of differences i n recombination frequency which occur from one host cell to another. Maize - - Experiments were designed t o determine the protection afforded by l a w oxygen tension against 1- and 2-hit chromosome aberrations in maize. linked genes on the long arm of chromoeome 3) was irradiated i n a i r and N2 atmosphere and used to pollinate teeter plants homozygous receasive mutant kernels. Whole seed losses of A and Sh arise as a result of inter et it i al deletions (2Lhit) b r teFnzindl deletione (1-hit) where Chromosome breakage was detected by the occurrence of

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the break is proximal t o the A-Sh- - regian. both dominant and recessive tissue arise almost entirely from terminal deletione ( 1 - hit) where the break is distal to this regia. protection was obtained for the whole seed losses, where aBa 9.9-fold protection was found f o r the mosaics. initial breakage hypothesis which has been presented t o explain the mechanism of the oxygen effect, and strongly suggest that the e f f e c t 16 exerted on the recovery process. Kerneb which are mosaic for Them data do not agree with the Similar experiments were conducted using onion root tips. Anaphase bridges were scored i n root tips fixed 48 hours after irradiation in air double bridges by a factor of 1.9 while the single bridges shared a 9.5fold reduction. Since the chromosome8 in the scored cells were undivided a t the time of irradiation, the single bridges resulted from terminal deletions ( 1 - h i t ) and the double bridges from dicentric and r i n g chromoB O ~ S( 2 - hit). Thus the data obtained for both maize and onion are in Irradiation in nitrogen decreased the frequency of Neurospora -- In Neurospora it has been possible t o reveal the princ i p a l locus of action of radiation through the use of genetically tagged hsploid nuclei within a common cytoplasm. Cultures gram i n this condition of heterokaryosis produce multinucleate cells containing the marked increasing dose of radiation i n the manner which would be expected if The nuclear composition of these cell sir r found t o change with

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ti ve relation between the nuclear changes and the total cell survival ratio share that the effective X-ray damage i n Neurospora i s wholly on the nuclei up t o dosee of atleast l70,OOO r. In addition to this dominant nuclear effect, receseive mutations have been studied. These cfAn be carried i n the heterokaryotic cultures, but are l e t h a l as soon as they become homokaryotic. Even on complete msdium over 9C$ of these mutatiom a r e lethal when homokaryotic. Thus the class of recessive lethal mutations involves a much larger number of genetic loci than does the clam of biochemical mutants. Teste for all elis m of the separately induced receesive lethals ehow that they are BO rarely allelic that they cannot contribute significantly to the lethal effect of X rays on multinucleate cells. ual nuclei is high enough, however, t o contribute measurably t o the lethal Their frequency among individeffect on uninucleate cells. Tradescantia - A study of the pre tre a tmnt of X-rayed Tradescantia chromosomes w i t h infrared (ca. 9600 A ) has shown that the magnitude of the infrared effect, which increases the frequency of chromosolils aberrations, i e strongly dependent upon temperature, and to a less marked degree upon ion density. The infrared effect cannot be consistently obtained when the temperature of the c e l l s during infrared exposure is above 20-22OC. A t O°C, approximately 5@ increase i n aberratiun frequency is obtained, a Ilpuinnun i s reached a t l2OC (ca. 15% increaee), followed by a gradual decrease t o no effect at 20-22OC. It seems clear that the state induced i n the chromosomes by infrared is temperature sensitive, but the complex

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nature of the temperature curve is not colapletely explained by this e-10 point of view. When combined with gamma rays, 250 or 100 kvp X rays, a given amount of infrared has a greater e f f e c t as the ion deneity of the subsequent radiation is increased. With neutrona, however, a similar effect does not seem t o hold although this ccmclusion i e baaed on but a Combination of pro- and poettreatments of infrared together w i t h , 100 kvp X =ye, in dha tse that any given dose of X rays produces, in additic m to a component of visible aberrations, a finite number of sites of potential breakage i n the chromosomes which can be acted upon by the infra red. The mnchanism by which infrared acts cm thee0 sitee is not understood, however, although it has been shown previouely that the e f f e c t s of infrared, given asa pro- or post tre a tmnt, can be wiped out by a temperature shock. Furthermore, the fact that the time interval between expoeuree t o infrared and toX rays i s of relatively little importance indicates that the state induced by infrared is relatively stable at room temperatures.

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IIBECT CYTOLOGY AIVD GXHXTICS 7 (Biology Division, Oak Ridge Rational Laboratory) Presented by Mary E. Gaulden The Urge neuroblast8 of grasshopper e dry os in living cultures are wed t o study the effecte of radiation on c e l l structure and mltotic rate. Further, we are attempting t o correlate these effects with radiation-induced alteration8 in the physiological and biochemical processes of the mitotic C e l l . It has been fotmd that propha88 i s the 8enBitiVe stage Of mito sisto icmizing radiation and that ita retardation i s associated witha visible change i n the chromosomsa. variee t o some extent with the kind of radiation, 8.g. , 125 lrvp X rays cause greater mitotic inhibition than P32 f3 rays. The response of propbase t o radiation The effects of X rays on prophase can be mitigated by reduced oxygen tension and by yolk factors. Biochemical studies indicate a poait ive correlation between radiation-induced inhibition of nucleic acid synthesis and inhibition of mitosis a t low doses of X rays. The group worklng with Drosophila is concerned not only with the effeot of radiation on genetic msterial but with basic genetic problem as well. During the l a s t several years the following problem received

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rather extensive investigation: spew and spermtogonla, (3) e f f e c t of temperature on ipaUCti0.n of mceseive lethal s, (4) effect of hydrogen sulfide on radiosensitivity of recessive lethals, (5) mechanism of the oxygen e f f e c t as seen in studiee of recessive lethals, daninant lethals, chrmoscme translocatioxu, and ring cbromosop~s, (6) the genetic b a s i s of saraatic variegation, (7) chrc~aoecars segregation in aneuploid Drorophila, and (8) effect of cyclotron neutrcme and neutrons from nuclear weapon detonations on induction of dominant (1)A re true point mutatiana Induced by (2) induction of specific l o c i nntatione in mature problems are continuing.

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(Biology Division, O a k Ridge National Laboratory) Presented by John R. Tatter Badlation Protection - Previous findings show Xecherichia coli to have a partial recovery after X irradiation U incubated for short period8 in a medium composed of queoue extracts of various tissues. and ident if ica tian of necessary factor(a)for this increased viability of irradiated bacteria are being attempted. The mammalian spleen has been found t o have the highest specific activity of any tissue tested. this recovery factor bears any relation to the factor which is respoasible for post ir radi a tim recovery in mmumls remains t o A study of the effect of several different incubation temperatures cm t h e inductim of reverse mutatians in an X-irradiated purine-requiring a …