Document text
Machine-read from the scan, so expect some errors. Lines that couldn’t be read are left out.
Page 3
V. C e l l Dlvieion aad CeU Size After Lethal Doses of x-Rqs in Microorganisme
Page 4
The principle activity of the ph;ysics Section daring this report period has been orre Oi mceto the CUcal Section. tenance Of the -, wistance in treatment planning, and canstruetion ai devices to fadlitate the treatment of patients are the main atep i e s involv!ed. Tawmb the ma of the report period, the patient-treatme& program was dlnccmtirmcd tempor- BO that attention has been glven t o aaae other matters oi We8t. The vacuum calasimeter, which hae been used several times pffvlcarsly A trananiasian monitor which adds 1.0 mm Al t o mea~urethe radiation output fran the synchrotron, was iastalled under t o the jnhereni, filtration has been installed and adapted t o operate into a Radocon. The enerw output in a given f i e l d size has been determined relat i v e t o the integration unit of the Rn&con by the calorimeter for faur x-ray by prlmmy and secmdnq lead collimating plates and has a dieaneter of approJdmately 5.0 on at the surface of the calorimeter absorber. studied for cach qadlity by malrlnp a rattable erposure on Eastman Induetrial X-Ray Film, !l?ype M, and assunlng that density above fog IS a suitable IndiCstar of radiation L & e ~ i t y . Alp0 by filme, the exact poeitian with LFa Victor een thinrble r-meter. erpoaurea in af three thimbles (each were made in relation t o the integralmonitar+ngunlt iroln the rad oca^ The fFlm data enable the i at emit yd i atri but i ~acros~the field to be 1~ h t e d to that in the reeon sampled by the thimble chamber. !l!his gims a Since thc cazcnlmetv measurement gives ergs per monitor unit for the eane field, diviaian give. beam energy requFranent to protiwe a rantgen. 100 h c p , 110 filter added, and 250 kvcp for each of 2 mm Cu + The field is determined Subsequently, the dietr%butionof radiation across WSf i e l d vae 8- to the Of th+ field YBB d e t m d f0.T the stMitiPe W- Of -ty the beem -Q.t8 b aboprt Oefi
Page 5
X-Ray Filter Beam Energy -rent filter ULb t o be 2 nnn Al, t o which the dtor adds During the next report period a etudy will be made of the dietribution of energy absorption in a water bath which, when combined vith the calorimetric detemlnation af beem energy, VFIl glve an experimental determination of abaorbed dose in water. This method, aa appUed t o the eynchrotran, has been described previouly (Ea-14, and eleevhere). The ferrow suUateAenzoic acid dosimeter continues t o be used aa a s-ze the smutron output monitor t. Absorbed ~ e snear 600 give a bneity change of 0.10 at 2602 Pwity fluctustiom for a avtn monitored expwure over several mnntb b a ~ every sem 1s It hes been wd aaily, prior t o patient treatments, t o
Page 6
A systematic evaluation of the rsbtatioa-induced changes in sane to met uw integral doses delivered by rel at i ~ eel yBmBu kenre to Jar& As stated above, moat of the actual operetion of the synchrotron has bten in connection vith the patient-treatment progrem. ment rediof'requency power rptem and the very successful t e s t it epjoyed. permit installation oi thi. DCV system sad relegation of the present one to The anly notable S m of .QY other critical components have also been !bnzble-wi.e, there ham been consi&rable annoyance from an unexpected rmce - the irrar refri ~ a t mfar the vacuum system. caused the only caaccllrtlm of a patient-treatment day which has been ouf lot to date. chrotron &put is now abaut half ai w h a t it should be. 4 e c t a r e is being developed and an emission-testing unit la being construeIn fact, thie trouble our 4cctors are b e g b n l q to show their age, and so the synA wurce of new
Page 7
Some Gross and Hietologic Aspects of the Developnent of Morbidity Prior t o the Terminal State, With Special Reference t o the Gonad, Uterus, Heart, Liver, and Submaxillary Gland When the preaent rtudice were initiated several years ago, a consic+ erable body of information wan available concerning both the acute and thk late changes that occur in laboratory animals after whole-body exposure t o external sources of ionizing radiations. By now this work has been extenexamining the animals long mer eqoeure, usually i n the terminal state or Immediately after death. or two after exposure. able, however, concerning the changes in rurviving animals during the "intermediate" period, i.e., the period that follows the subsidence of the acute reaction and precedes the terminal s t a t e . The object of our studies w a s t o contribute such information for CAFl mice and closely related Information f o r W / c mice, both rully mature at the time of Irradiation. have mentioned some of our fi&,ngs in previous reports (UCSF-ll, UCSF-13). The folloving is a brief slmrmary of the completed project. Mature CAFl and BALB/c mice (average age 145 days) were Irradiated The animals a.Uve at the end of the acute period of reaction, 7 weeks a f t e r exposure, were distributed into experimental groups for serial sscrifice and the study of eunrival. The late changes were determined f o r the most part by The acute changes were studied during the month Relatively little specific information was avail- *Present address: Departnent of Radiology, Stauford University, School of Medicine, san fi811cisc0, California. Fort Sam Houston, Texas. t be sent address: Headquarters, Fourth U. S. Army Medical Iaboratory, *Cancer Research Genetics Laboratory, University of California,
Page 8
In the CAF1 series, the median age at death wae not influenced by That of the controls wa6 885 days; tbat of the Irradiated ed mala ,e x . for at least one year efter exposure. The intermediate period w a s defined aa the interval between the subsidence of the acute reaction and the attainment of lo$ cumubtive mortaUty. Attention wa8 focueaed on the develop nt of marbldity during this period. Grosa and microscopic examination revealed the follawing principal chsnges in the CAF, hybrid at about the cloee of the Intermtdiate period (330 days after exposure; age 490 w). 683 d q s (survival time, 543 aays). More than 9 6 of a l l mlnulE llved In the thymus, gaads, and uterus, a eignificant net loss of mabstance had occurred. frr mrizTediated animals, the female thymus vae beavier than in the malej in irradiated mima3.s , the reverse wae true. In the testes, irradiatian inuraeed arteriosclerosis and the incidence of material in the l nter et ltl al cells that staFned vith the Schiff-reagent V e r y feu t- YCTC detected grossly in the thymus, gonads, and \, uterus, but microscopicaUy two-thirds of the ovaries showed evldence of neoplasia. The appearance of pulmonary tumors was slightly accelerated in the male. The male hartJ kldney, and s m w gland were smaller than i n This resulted fipm failure t o increase in sizecontrols of the a t the normal rate during the. intermediate period, not frmna loss of sub- 'REf d e Iridnuy aad eutm8xIllary glands, a g u that show re& -am in the ~LALOC, were un med in wight, although masculinized tol logic ally. !be diiferenccs in Height between the male and female heart, liver, kidney, Bnd 1 3 - q glauds, organs knovn to be sensitive t o the mabollc effect of testosterone, were reduced. In the -gateJ a principal reault of the above -6 was t o The incidence of lene opacltics wae very Lav, a l t h w it increeeed in propartion t o time and dose. muty had reached about 3%. !be flndlngs were similar to those for It YBB cou al wd that a state of morbidity +dependent of neoplasia The state develops as the result
Page 9
of the complex interplay of topical and abscopal effect6 and involves a change in endocrine balaace. essarily affecting survival. It i s suggeeted that honnnne therapy might
Page 10
It is the object of this note t o campare three met- of treating the llfe-table data of irradiated and unirrsdiated mice. The data were obtained irOm the serial wzriiice study sunmarized i n the preceding section (I), a 8tudy not primarily designed t o provlde U e - table data but adapted t o do 80. The animah had been irradiated at about 145 day6 of age, and by x)o drye of age the prompt death rate had dropped t o zero. For the present analysis, the table was constructed on the basis of the napant89tc9LB" death. tht occurred &er 200 d a y s of age, due allowance bvlng been made for th rapdomly selected animals sacr s iced for special exeminatione, ueually before 500 -6 of age (Table I). The data for both sexes were pooled since the differences betveen them either we& amall ar were not statistically significant. fP Table I. Nu uber of Animals Used t o Construct Mortality Table *Alive at age 200 daya.
Page 11
Saeher, YBB defined as the log of the death rate; it is plotted ae a f m a - tion of age in Fig. 2. Ilh Cbnpertz function will k represented by a horizontal Ilne BCTOBB the graph if tbe death rate l a const&&. rate hcreases ata conetaut rate, the function wlll be aetrw lFne whoee slope represents the acceleration of the death rate. Oampertz functions In Fig. 2 nray be divided iDt0 two parto after agc 450 mately linear and parallrl, tbat far the irradiated population being &ISplaced t o the lert Of that for the cantrolrr by abarrt so aay. QT 8(1. In thiIi t e r about age 650 tha cumw r- the irradiated and control populations arr no laager truly linear and t h y divere 80 that a t death rates of 4 6 or If the death
Page 12
Fig. 1. Per cent sur vln rl aa a function of The CAFl mice were irradiated at M average of 145 dqys. !be s u r v ~ wpopulation at 200 -6 of age takenarr 100%.
Page 13
a8 a function of age. The death rate wss expressed ae the per cent of anbah dying per 50 d a y s .
Page 14
Fig. 3- Cumulative per cent mort u ty (probability ecale) as a function of age.
Page 15
an.fmnle the diphasic nature of the function m d rtrihiag. The difference between the control snd Frradiated alopes YBB marlrcd. this function for dealing with the mortality table of therapeutically Frradiated patients, and it n o w appears t o be of couaiderable interest for Tivey haa wed We plan t o examine the utility of these 6nd other methode for analyzing the life table of the control and irradiated mice entered in exprirpents describd in tbe fducnring eection (III) oi tbis report. *H. Tivey, Prognosis for swi val Fa leukemlaa of chilbbood. Mar of the literature and the proposal of a simple method of reporting s uml val data far these diseases. Pediatrics 10, 4&59 (1952).
Page 16
III. EFFECT OF x-RAYEWQSURE ON TBE LIFE !i!ABIz OF TBE MDZPGE -- PLAA The U e of the muse, like that of other mammals, w be divided into fithaugh the period of U e (4)post-puberty, (5) m tur it y,(6) senescence. in which an x-ray erpoeure occurs, or in which exposure is initiated, may p 4 a major role in det- the nature of subsequent changes, little attention has been paid t o this factor in s t d i e s dealing with the effect of x-rw on the life table. Usua;lly "young" mice in perioda 3 and 4, 6 t o 12 weeks old, have been used. In our previaue rtudy n con8tructcd the Ufe table of the mature CAF moue irradiated with 250-hx-rqs at age 145 d a y s . Experiments (TablyISt now in progress o r abaut t o begin are designed t o provide information relating t o the following questions: (1) Do x-rays modify the life table of the mature aninal in dem ntl y of the age at which exposure occursf and senescence extend f i c n n abut 125 t o 880 days of age - the latter is the median Ufe span. In CAF, mice the periods of maturity (2) what, if any, is the effect af fractionating the exposure t o x-ra;yet Little is known conce- the effect of partial-body irradiation OD the LUe table of the mouse, or of eay other auimal. therefore been started with U t CAF, mice. and abdanen), each about 2 an long, an expoeed t o 250-h x-rays w h i l e the an- -are uader Ught nanbutal Bnesthesla. It i s planned t o enter about 35 males and 50 female8 in each experimental Syetematic studies have Three regions (in head, tharax, Thc tissue W e s are 575 aud 900 r. %is study isa collaborative one with Dr. De-, Cancer Research k ne tics bbaratary, university of callfornia, Berkeley.
Page 18
Since the number and vmiety of tranaplantable r a t tumors Is somewhat limited,' we have looked for transplantable tumnrs in the rats maintained in this laboratory. The lines of rats were originally isolated by Dunning anti ~ urtis ~ ~ ~ and are currently maintained by Dr. Wilhelmlna Dunning of the University of Miami,at Coral Gables, Florids. I n December, 191, we obtained Fischcer Institute, and A x C/9935 (Irish Agouti) breeders, 38th generation, from Dr. Dunning. The Flscher r a t breeds prolifically but, i n our colony, I s subject t o pulmonary infection with abscesses, presumably of virus origin, which becanes chronic, is grossly evident sometime a f t e r 1 year of age, and i s probably the principal factor limiting survival. 9935 (Irish Agouti) rat is mOre difficult to breed, but is not especiall$ susceptible t o pulmonary infection. vantage of each of these lines, ne have usually employed the hybrid,' designated FAC(I)F,, obtained by crossing A x C males with Fischer females. To circuwent the particular disadAll the m hals in the colony after weaning are fed only Purina LabDuring the first week after weanoratory Chow Checkers except nursing mothers who receive a daily supplement of milk, cod liver oil, and yeast. ing the drinking uater of the young animals is supplemented with terramyline t o be less than 13 months.' We found the median age at death of 10 males t o be 22 months (range 16-25) and of 9 females t o be 25 (1&?7) tributable t o the fact that OUT animals in this particular experiment received 30,000 units of penicillin (subcutaneously) at age 3.5 months, end Dunning and Curtis found the average life span of the Fischer/% The striking difference i n the two …
The text continues in the original scan (32 pages).