Dose Of Whole-body X-irradiation Research Articles

Parthenolide Selectively Sensitizes Prostate Tumor Tissue to Radiotherapy while Protecting Healthy Tissues In Vivo.

Radiotherapy is widely used in cancer treatment, however the benefits can be limited by radiation-induced damage to neighboring normal tissues. Parthenolide (PTL) exhibits anti-inflammatory and anti-tumor properties and selectively induces radiosensitivity in prostate cancer cell lines, while protecting primary prostate epithelial cell lines from radiation-induced damage. Low doses of radiation have also been shown to protect from subsequent high-dose-radiation-induced apoptosis as well as DNA damage. These properties of PTL and low-dose radiation could be used to improve radiotherapy by killing more tumor cells and less normal cells. Sixteen-week-old male Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) and C57BL/6J mice were treated with PTL (40 mg/kg), dimethylaminoparthenolide (DMAPT, a PTL analogue with increased bioavailability) (100 mg/kg), or vehicle control three times over one week prior to combinations of low (10 mGy) and high (6 Gy) doses of whole-body X-irradiation. Tissues were analyzed for apoptosis at a range of time points up to 72 h postirradiation. Both PTL and DMAPT protected normal tissues, but not prostate tumor tissues, from a significant proportion of high-dose-radiation-induced apoptosis. DMAPT provided superior protection compared to PTL in normal dorsolateral prostate (71.7% reduction, P = 0.026), spleen (48.2% reduction, P = 0.0001) and colorectal tissue (38.0% reduction, P = 0.0002), and doubled radiation-induced apoptosis in TRAMP prostate tumor tissue (101.3% increase, P = 0.039). Both drugs induced the greatest radiosensitivity in TRAMP prostate tissue in areas with higher grade prostatic intraepithelial neoplasia (PIN) lesions. A 10 mGy dose delivered 3 h prior to a 6 Gy dose induced a radioadaptive apoptosis response in normal C57Bl/6J prostate (28.4% reduction, P = 0.045) and normal TRAMP spleen (13.6% reduction, P = 0.047), however the low-dose-adaptive radioprotection did not significantly add to the PTL/DMAPT-induced protection in normal tissues, nor did it affect tumor kill. These results support the use of the more bioavailable DMAPT and low-dose radiation, alone or in combination as useful radioprotectors of normal tissues to alleviate radiotherapy-induced side-effects in patients. The enhanced radiosensitisation in prostate tissues displaying high-grade PIN suggests that DMAPT also holds promise for targeted therapy of advanced prostate cancer, which may go on to become metastatic. The redox mechanisms involved in the differential radioprotection observed here suggest that increased radiotherapy efficacy by DMAPT is more broadly applicable to a range of cancer types.

Macrophages mediate adverse effects of cholesterol feeding in experimental nephrosis.

We tested whether the deleterious effects of hypercholesterolemia, in a progressive glomerular disease model, may be mediated by infiltrating renal macrophages. A single sublethal dose of whole body X-irradiation (XI) delivered to rats with acute puromycin aminonucleoside (PA) nephrosis fed a high-cholesterol (HC) diet resulted in significantly greater inulin and p-aminohippurate (PAH) clearances at 11 days after PA without any alterations in circulating lipid levels, in contrast to nonirradiated HC-fed nephrotic controls. This functional protection was associated with significant declines in both glomerular and cortical interstitial macrophage number. Over the course of this 16-wk model, HC-fed PA rats had significantly less albuminuria as well as significantly fewer glomerulosclerosis (GS) lesions and less mesangial matrix expansion at the end of the study despite an equivalent degree of sustained hypercholesterolemia. This data suggests that reducing the infiltrating glomerular and cortical interstitial macrophage burden with XI during acute PA nephrosis, unaccompanied by any hypolipidemic effect, produces not only early salutary effects on renal function but also a significant amelioration of the progressive glomerulopathic features of this model. This is consistent with the hypothesis that the infiltrating renal macrophage, in large part, directly mediates the adverse effects of hypercholesterolemia in this model.

EPR study of mouse tissues in search for adaptive responses to low level whole-body X-irradiation.

Effect of a low dose of whole-body X-irradiation (D1 = 0.075 Gy) of mice on some biochemical changes induced in the spleen and thymus by a subsequent challenge dose (D2 = 1.5 Gy) was studied by electron paramagnetic resonance (EPR). Kunming and SHK mice were used. Concentration of ribonucleotide reductase (RR) in the spleen and thymus of unirradiated Kunming mice was 0.70 and 0.46 microM respectively, and of unirradiated SKH mice--0.37 and 0.21 microM respectively (systematic error 45%). For mice exposed only to the low dose (D1 group), a stimulating effect on RR activity in spleen and thymus was found, while in mice subjected only to the D2 dose (D2 group) activity of the enzyme in the organs decreased considerably 18 h after irradiation. The group of mice irradiated with D1 and D2 doses, given at a 6-h interval (D1 plus D2 group), showed a RR activity in the organs lower than D1 and higher than D2 groups. This finding indicates that there exists an adaptation-like response to a low-dose whole-body irradiation in murine spleen and thymus. This low 'inductive' dose makes the organs' RR less susceptible to inhibition induced by a subsequent challenge dose. Preliminary results showed that the same kind of response is probably a characteristic of the RR content of splenocytes as well as of the rate of thymidine incorporation into splenocytes. 5-Thyml radicals of DNA (TH radicals) induced in whole tissues by gamma-irradiation in vitro at 77 K were also studied. Radiochemical yield of these radicals (4.0 and 5.3 nmol j-1), for spleen and thymus respectively of unirradiated Kunming mice, and 2.3 and 2.6 nmol J-1, for spleen and thymus respectively of unirradiated SHK mice (systematic error 30%), decreased significantly in both organs upon D2 irradiation. This decrease, however, was the consequence of DNA content diminishing upon D2 irradiation rather than change of DNA radiosensitivity: the beta value of TH radicals, i.e. yield of radicals per unit mass of DNA in each organ was equal for the mice from all D1, D1 plus D2, D2 and control groups. The beta values of TH radicals in mouse spleen and thymus were of the same order of magnitude compared with the yield of the single-strand breaks of DNA measured previously in rat organs just after whole-body irradiation, i.e. about 1 x 10(2) (Gy x 10(12) Da)-1.

The action of azimexone on the cells of the hemopoietic system in mice, especially after damage with X-rays.

Mice were exposed to single doses of whole body X-irradiation (1 - 2 - 4 Gy) or were treated with sulphur mustard (15 mg/kg body weight i.p.). This treatment caused a reduction of the pluripotent stem cells in the bone marrow, of the total count of nucleated bone marrow cells in the femora and of the WBC in the peripheral blood. The size distribution of the bone marrow cells showed three separate peaks. From the histological examination of the bone marrow of X-irradiated mice it was deduced that the first peak represents erythrocytes, the second lymphocytes and the third peak the precursors of red and white blood cells. Multiple doses (25 - 50 - 100 mg/kg body weight) of azimexone, an immunomodulating substance, led after moderate doses of X-rays (2 Gy) or sulphur mustard to a more rapid recovery of the various parameters. In particular a stimulant action of azimexone on the pluripotent stem cells of mice not subjected to the injurious agents could also be demonstrated.

Effect of Two Graded Doses of Whole-Body X-Irradiation and Radioprotection by the Use of S-Phenethyl Formamidino 4 (N-Ethyl Isothioamide) Morpholine Dihydrochloride

The protection offered by a newly synthesized compound (S-phenethyl-formamidino-4(N-ethyl isothioamide) morpholine dihydrochloride) against radiation effects on DNA, RNA and protein biosynthetic processes in the brain, and on metabolites of 5-HT and nor-adrenalin, i.e., 5-HIAA and VMA, in the urine, including the radiobiological damage to thyroid and testes, was evaluated. The use of the compound prior to irradiation prevented radiation-induced changes in the thyroid and testes. The radiation-induced alterations in the pattern of DNA, RNA, protein in the brain, and in 5-HIAA and VMA in urine could be averted by treatment with this compound prior to each dose of X-irradiation.

Depression of T lymphocyte function in chimpanzees receiving thymectomy and irradiation.

SUMMARY In studies analogous to those in which the thymus dependency of immune functions in murine systems was determined, three chimpanzees were thymectomized, splenectomized, exposed to lethal doses of whole body X-irradiation with limited bone marrow shielding, and subsequently evaluated for lymphocyte markers and functions over a period of years. In the oldest animal studied (Irena, 7.2 years at surgery), the percentage of peripheral blood T cells decreased to about 60% of control values and remained at that level for approximately 11/2 years before returning to normal. In the two youngest chimpanzees (Adrian and Boris, 1.7 and 2.2 years at surgery), T cell rosette values dropped to 15 to 40% of control values after irradiation. T cell percentages in one of these young chimpanzees (Adrian) returned to about 75% of the controls 11/2 years after X-irradiation. Phytohemagglutinin and concanavalin A mitogen responses were less affected in the oldest chimpanzeee. However, even in the oldest animal, the responses to phytohemagglutinin and concanavalin A began to show a gradual and consistent decline 11/2 years after irradiation. Mixed leukocyte culture responsiveness was most affected by the experimental procedures, being greatly reduced in all three chimpanzees during varying time intervals. In general, the effects of the experimental procedures used to produce T cell deficiencies varied with the age of the chimpanzee at surgery, the time after irradiation when the animal was tested, and the lymphocyte marker or function studied.

Regional blood flow in rats exposed to supralethal doses of whole body x-irradiation.

Relative blood flow in different organs of the supralethally (3 kR) whole body X-irradiated rat was studied using labeled 15 mu microspheres. Immediately after irradiation blood flow in brain diminishes. From 10 to 20 hrs a phase of increase in blood flowing to many parenchymal organs ensues. A second maximum 45 to 50 hrs and a third one at 60 hrs. In most organs except in brain and liver relative blood flow diminishes before death. The genesis of these changes as signs of a slowly developing shock is discussed.

Epidemiological and pathological studies of reticulum cell sarcoma in mice (C57BL-Cne x C3H-Cne)F 1

Life-long observations on untreated animals have shown that spontaneous reticulum cell sarcomas (RCS) developed in 56.5 % male mice of the hybrid (C57BL/Cne x C3H/Cne) F1 strain; the average age at death of mice with tumors was 949 days, compared with 929 days for all causes: no age-specific peak of mortality has been shown to occur over the entire life span of the animals. Histologically, the spleen and all the lymphnodes, including the mesenteric node, were always invaded; neoplastic growth was found less frequently in kidneys, liver and lungs (77, 70, and 40%, respectively), only occasionally in other organs such as adrenals and testes, and never in the thymus. The tumor was predominantly composed of a single type of neoplastic cells, resembling highly undifferentiated reticular cells, typically proliferating from the periarteriolar region of the lymphatic follicles in the spleen. The monomorphic aspect of the tumor cell population suggests that RCS in this strain of mice may be classified as type A according to Dunn. Electron-microscopy observations showed the presence of a few virus-like particles both in tumor cells and in sediments from cell-free extracts. Transplantation of cells from spontaneous RCS into both normal and lethally-irradiated syngeneic recipients was successful only in 4 out of 7 experiments, regardless of the tissue of origin of the neoplastic cells (spleen, lymphnodes or bone marrow). Virus-like particles were seen with higher frequency in transplanted tumors. Inoculation of cell-free extracts into neonatal mice of low-leukemia strains has not so far been successful. Splenectomy of young animals as well as the intravenous injection of syngeneic bone marrow cells immediately following a lethal dose of whole-body X-irradiation significantly reduced the frequency of spontaneous tumors.

Acceleration of Lymphoid Tissue Regeneration in X-Irradiated CBA/W Mice by Injection of Thymosin

Thymosin, a lymphocytopoietic preparation obtained from calf thymus, was examined for its effect on the rate of regeneration of lymphoid tissue in CBA/W mice exposed to whole body x-irradiation. In CBA/W mice receiving either an acute (400 R) or a lethal (700 R) dose of whole-body x-irradiation, thymosin was found to have a potent stimulatory influence on lymphoid tissue regeneration. Administration of thymosin daily, beginning at 1 1/2 hours after irradiation of the animals, significantly accelerated the rate of weight increase and3 H-thymidine or ${}^{3}{\rm H}\text{-deoxycytidine}$ incorporation by spleen and pooled brachial, axillary, and inguinal lymph nodes. Animals treated with thymosin daily for 7 days prior to being subjected to x-irradiation had, initially, larger lymphoid structures which were less severely involuted by radiation and exhibited an accelerated rate of regeneration subsequent to exposure to x-rays. Radio-autographic sections of the lymph nodes and spleens of the thymosin-treated g...

Early Increase in the Miscible Deoxycytidine Pool in Rats after X-Irradiation

Abstract : Intraperitoneal and intravenous injections of tracer quantities of 3H- or 14C-labeled deoxycytidine (CdR) were used to investigate the biologic half-life, the miscible pool size, and the turnover rate of CdR in normal and X-irradiated rats. The specific activity of highly purified CdR isolated from blood plasma samples taken at various times after injection of the tracer CdR was used as the basis for calculating these values. The mean values observed for normal rats were: biologic half-life 116 minutes, miscible pool 790 micro g/rat (100 to 180 g), and turnover rate 7.0 mg/24 hours/rat. The miscible pool of CdR appeared to be non-uniform, with the intracellular concentration appreciable higher than the general body-water concentration. About one-third of the total miscible CdR appeared to be intracellular. After relatively low doses of whole-body X-irradiation (25 to 100 rads), there were alterations in the turnover kinetics of CdR, but the presence of non-steady state made computation of the above three values impossible. However, the data are fully consistent with an increase in the miscible pool size of CdR, occurring as early as 1 hour postirradiation. The data do not provide information as to the mechanism for this apparent increase. (Author)

Enhancement of Murine Ascites Tumor Cell Killing with X-Irradiation by Thiol Binding Agents

Female mice bearing the Ehrlich carcinoma or P388 lymphocytic leukemia tumors in ascites form were given sublethal doses of whole-body x-irradiation and the thiol binding agents N-ethylmaleimide, hydroxy-mercuribenzoate, or iodoacetamide, injected intraperitoneally prior to irradiation, as a single treatment. These compounds were found previously to sensitize mice to radiation lethality. Enhanced tumor cell killing was observed as measured by tumor cell count, along with slightly longer survival times of the host animal. Increasing the dose of either radiation or drug alone also caused an increase in tumor cell killing, but at the expense of earlier mortality of the host animal. At the doses employed the sensitizers examined appeared more effective on these two ascites tumors han on the host. The mechanism of enhancement of radiation killing of tumor cells by these drugs is not clear, although it appears not to be due to additive toxicity effects. Similar experiments with several cancer chemotherapy agents showed that those compounds did not act as radiosensitizers.

Sensitivity of Acatalasemic Mice to Acute and Chronic Irradiation and Related Conditions

Acatalasemic mice are no more sensitive, as measured by lethality, than normocatalasemic mice to acute whole-body x-irradiation, chronic whole-body gamma irradiation, or exposure to one or several atmospheres of 100% oxygen. If the animals receive a preliminary injection of aminotriazole, which reduces the catalase activity of all solid tissues but does not affect erythrocyte catalase, the acatalasemic mice are rendered essentially acatalatic, but are still no more sensitive to the agents and procedures listed. In fact, the data suggest that low body catalase, far from being deleterious, may actually be protective to an animal receiving a single dose of whole-body x-irradiation. On the other hand, the acatalasemic mouse is considerably more sensitive to injected hydrogen peroxide than is the normal mouse, and prior injection of aminotriazole further increases this sensitivity.

Hemopoietic colony studies. V. Effect of hemopoietic organ stroma on differentiation of pluripotent stem cells.

In heavily irradiated mice, bone marrow regeneration of either endogenous or exogenous origin was shown to occur in discrete foci comparable to the more intensively studied spleen colonies. The number of endogenous bone marrow colonies was inversely related to dose of whole body X-irradiation. Endogenous marrow colonies were found after higher doses of irradiation than were endogenous spleen colonies. Most of them were granulocytic in nature. Exogenous bone marrow colonies in lethally irradiated mice injected with bone marrow cells were proportional in number to the dose of cells injected, appeared at a time comparable to spleen colonies like which, at 7 or 8 days, they were of single differentiated cell line, either granuloid or erythroid or megakaryocytic, with a small percentage of "mixed" colonies. Whereas erythroid colonies outnumber granuloid colonies in spleen, either in situ or subcutaneously transplanted (E:G colony ratio of about 3.5), granuloid colonies outnumber erythroid in bone marrow (E:G colony ratio of about 0.7). The characteristic E:G colony ratios of spleen and marrow appear more likely to be the result of a hemopoietic organ stromal influence on pluripotent colony forming units (CFU's) than of selective lodgment of committed (unipotent) granuloid and erythroid CFU's in bone marrow and spleen, respectively, as indicated by the following. Bone marrow stem cells (CFU) which had reseeded the marrow cavity of irradiated primary recipients 18-24 hr earlier, were reharvested and retransplanted intravenously into irradiated secondary hosts. The E:G colony ratio of the colonies formed in the spleen of the secondary hosts was typical of primary spleen colonies (2.8), that of the colonies formed in the marrow cavity was typical of bone marrow colonies (0.6). Pieces of marrow stroma containing reseeded CPU's from the contralateral femur of these same primary recipients were implanted by trocar directly into the spleens of other irradiated secondary recipients. Those CPU's that developed in the intrasplenic-implanted marrow stroma yielded an. E:G colony ratio of 0.1. Those that migrated into the contiguous and remote portions of the spleen gave E:G colony ratios of 2.9 and 2.4, respectively. Irradiated marrow stroma and normal spleen CPU's (a 1 mm cube of spleen) were loaded into the same trocar and implanted directly into the spleens of irradiated mice. The spleen CFU's that migrated into the implanted marrow stroma yielded five granuloid and two mixed colonies. The larger number that developed in the host spleen yielded an E:G colony ratio of 2.9 or higher. Of those 19 mixed colonies that bridged the junction of spleen and implanted marrow stroma in each of the above two experiments, in every case, the erythroid portion of the colony was in the splenic stroma, the granuloid portion was in the marrow stroma.

Lethal Effects of X-Irradiation and Injection of Radioactive Phosphorus on Rats in Relationship to Age

The relationships between age and radiation sensitivity are of theoretical and practical importance from the standpoint of both radiobiology and the physiology of growth. Mice have been used as the experimental animal in most investigations of this relationship. As early as 1936, Furth and Furth (1) reported as an incidental observation that 5-week-old mice had a higher mortality than adult animals exposed to the same dose of whole-body X-irradiation. The first systematic studies were those of Quastler (2), who measured survival times in mice of varying ages after 800 r of whole-body X-irradiation, and Abrams (3), who employed the fraction surviving an exposure to 600 r as a measure of sensitivity. Formally determined values for a 30-day LD50 have been reported by Kohn and Kallman (4) and by Lindop and Rotblat (5). Although different measures of response and strains of mice have been studied, all these investigations are in essential agreement that a phase of minimum resistance to external irradiation occurs in this species during the fourth week of life. Less extensive data are available for other species. Casarett (6) has reported that 28-day-old rats survived only 4 days after 800 r of whole-body X-irradiation, in comparison to adult animals, which lived for at least 10 days after a similar exposure. Autopsy findings in this experiment supported the concept that tissue sensitivity was greater in the young animals and that Pathologic changes in various tissues of weanling rats became maximal at nearly the same time after irradiation. Kohn (7) found that 35to 40-day-old rats had an LD10 about 200 r lower than the value for adults. Kohlin (8, 9) has reported variations in survival time after whole-body irradiation of rats ranging in age from 1 to 3 days to 3 to 4 months and has presented

Protection of Mice against Irradiation and Tetanus by Homologous Bone Marrow Cells from Hyperimmunized Donors

Abstract Aside from irreversible damage to certain organs, such as the lens of the eye and the gonads, animals treated with lethal doses of whole body x-irradiation and protected by isologous bone marrow survive long periods without special care. Those animals protected by homologous bone marrow and other homologous tissues may have a different fate (1). The difference in mortality observed has been related to the histocompatability genes possessed by donor and host as described by Counce et al. (2). This situation is simplified when skin grafts are exchanged between a variety of inbred mice. In such experiments homologous skin grafts between mice that possess the same H2 genes remain viable for longer periods than homologous grafts between mice from different H2 groups (2). When homologous marrow is infused into an irradiated host the situation is more complicated; after surviving the acute effects of total body irradiation, the mice experience a second period of weight loss followed in some instances by dermatitis, diarrhea and death.

RELATIONSHIP BETWEEN THE DOSE OF WHOLE-BODY X-IRRADIATION AND THE URINARY EXCRETION OF 5-HYDROXYINDOLEACETIC ACID IN RATS.

SummaryThe dependency on x-irradiation dose of urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) in rats was studied. A significant positive correlation between the applied doses: 50, 100, 150, 200, 400, 600 and 800 r, and 5-HIAA excretion-rate, was found. By means of this biochemical test it is possible to discriminate between animals irradiated with ‘low’ (50, 100, 150 r), ‘medium’ (200, 400 r) and ‘high’ (600, 800 r) doses. The maximal increase of 5-HIAA output after irradiation appears during the first 24 hours; excretion returns to normal values on the third day after irradiation. The females show a more pronounced response to radiation than the males. The dose of 200 r seems to be the lowest that significantly increases the output of 5-HIAA. The rats pre-treated with sub-lethal doses (50–200 r) respond to the subsequent dose of 800 r with somewhat delayed reaction.Some other urinary substances showing a certain irradiation dose-dependency are compared with 5-HIAA; the latter appears to be a good indicator for the evaluation of absorbed radiation dose.

Protective effect of artificially induced hibernation against lethal doses of whole body x-irradiation in CF male mice.

Hypothermia induced by the use of neuroplegic drugs such as Hydergine, chlorpromazine or promethazine, followed by refrigeration, does not significantly enhance the protective action afforded by refrigeration alone against the lethal dose of whole body x-irradiation in CF1 male mice. The neuroplegic drugs, without refrigeration, provide a slight degree of protection, probably due to the slight reduction in the body temperature. It appears that the action of hypothermia as a protective mechanism depends not on depression of metabolism alone, but on a general depression of bodily processes. Urethane, in conjunction with refrigeration, appears to augment the lethal effect of x-irradiation in the CF1 strain of male mice.

Failure to induce immunological tolerance during recovery from irradiation.

NEONATAL animals and animals given large doses of whole-body X-irradiation are immunologically similar in two important respects: both are very poor producers of antibody, but both become satisfactory producers of antibody after several weeks, presuming that the X-irradiated animals survive. It is well established that during normal maturation animals go through a stage during which they may be rendered immunologically tolerant of certain antigens1, and it seemed of considerable interest to determine whether, following severe X-ray damage, a similar stage occurred during which tolerance could be induced by appropriate antigenic stimulation. As X-ray damage is followed by rapid proliferation and differentiation of mesenchymal cells, be they the animal's own or bone-marrow cells grafted from a normal donor, it seemed possible that there might be a stage during which potential antibody-producing cells could be modified by contact with antigen and rendered immunologically tolerant.

Induced tolerance and homologous disease in x-irradiated mice protected with homologous bone marrow.

SummaryCBA mice protected against an otherwise lethal dose of irradiation with isologous CBA bone marrow showed normal rejection of skin grafts from the Cb strain. Irradiated CBA mice protected with Cb or (Cb x CBA) F1 hybrid marrow were tolerant of skin grafts from the Cb strain. Irradiated CBA mice protected with a mixture of marrow from the Cb and CBA strain were not tolerant of skin grafts from the Cb strain. Late mortality (21 to 60 days post-irradiation), after good early protection (21 days) against doses of whole body X-irradiation above the LD100, did not occur in mice protected with isologous bone marrow (where neither the host nor the donor can react immunologically against each other). It occurred in mice protected with homologous marrow from a foreign strain (where both the host strain and the donor strain can potentially react immunologically against each other). It did not occur in mice protected with marrow from an F, hybrid of the irradiated strain (where the host strain can potentially r...

Susceptibility to Thrombosis in Normal Young, Aging, Cortisone-treated, Heparinized and X-irradiated Hamsters as Tested by Topical Application of Thrombin

Abstract 1. Thrombin applied topically to the everted cheek pouch of the hamster produced platelet and not red thrombi in exposed, uninjured blood vessels with circulating blood. Red thrombi were produced in stagnant blood. Thrombus formation occurred in the venules for the most part and seldom in arterioles or capillaries. 2. An in vivo test for platelet thrombus susceptibility, based on the thrombin reaction and the resistance of the hamster to thrombosis, has been described. 3. Thrombus susceptibility, measured by the thrombin test, increased with age and during cortisone treatment, and decreased after heparin injection and following large doses of whole body x-irradiation. 4. The thrombin susceptibility test could be correlated with the platelet count in x-irradiated hamsters, showing a relatively critical minimum concentration of blood platelets (100,000/cu.mm.) required for platelet thrombosis. 5. The relationship of platelet concentration to platelet thrombus formation and predisposition to hemorrhage has been discussed.