Pretreatment with 16, 16 dimethyl prostaglandin E₂ (DiPGE₂) provides effective protection against radiation and chemical injury. Cytoprotection against chemical injury is known to be influenced by sex factors, and is more effective in females than males. Since prostaglandin metabolism and biological responses to prostaglandin may vary between sexes, studies were conducted to compare DiPGE₂-induced radioprotection in male and female mice.
Pretreatment with 400 μg DiPGE₂/kg body wt substantially enhanced 30-day survival in males and females. There was no significant difference in the LD_50/30 of male and female mice receiving vehicle alone prior to irradiation, 8.34 Gy versus 8.46 Gy, respectively. DiPGE₂ treatment increased the LD_50/30in males to 12.1 Gy, providing a dose modification factor (DMF) of 1.45. Similar increases were observed in females, with a LD_50/30 of 11.6 and a DMF of 1.37. The reported difference in DiPGE₂-induced cytoprotection between males and females exposed to ethanol injury, and the lack of variation in the present radioprotection study suggests that separate mechanisms are involved in the two processes.

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Adult T-cell leukemia (ATL), induced by human T-lymphotropic virus type-I (HTLV-I), is endemic in Nagasaki, Japan. To investigate the effects of atomic-bomb radiation on development of this specific type of leukemia, 6182 individuals in the Radiation Effects Research Foundation (RERF) Adult Health Study sample in Hiroshima and Nagasaki were examined for positive rate of HTLV-I antibody. Several lymphocyte parameters were also studied for 70 antibody-positive subjects in Nagasaki. The HTLV-I antibody-positive rate was higher in Nagasaki (6.36%) than in Hiroshima (0.79%) and significantly increased with increasing age, but no association was observed with radiation dose. Whether relationship existed between antibody titer levels and radiation dose among antibody-positive subjects was not clear. The frequency of abnormal lymphocytes tended to be higher in antibody-positive subjects than in antibody-negative subjects, and higher in females than in males regardless of radiation dose. The lymphocyte count was lower in antibody-positive subjects than in antibody-negative subjects and lower in female than in male subjects. No evidence was found to suggest that atomic-bomb radiation plays an important role in HTLV-I infection.

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Relationship of cure and surviving clonogenic cell number after various doses of X-irradiation was examined in multicellular spheroids of LCT1 human lung adenocarcinoma cells, LCT2 human lung small cell carcinoma cells and FSA1233 mouse fibrosarcoma cells. Some of these spheroids were cured at such doses that considerable number of clonogenic cells still survived after irradiation. Radiocurability was analyzed by comparing total clonogenic cell number in spheroids, cellular radiosensitivity and critical cell number Nc, i.e., the minimum number of clonogenic cells required to produce regrowth. (Nc-1) cells were killed by post-radiation processes and the larger the critical cell number, the more radiocurable. The LCT2 spheroids had the largest critical cell number and were most radiocurable. To investigate underlying mechanisms, modifying effect of heavily irradiated (HIR) tumor cells on the clonogenicity, i.e., plating efficiency of unirradiated tumor cells was investigated. Plating efficiencies with HIR cells showed significant decrease in LCT2 cells, no change in LCT1 cells and increase in FSA1233 cells. The results indicated that in case of LCT2 spheroids some of viable cells, surrounded by dying or dead cells might have been killed with unknown toxic effect additional to direct irradiation effect. Thus, critical cell number analysis may be useful to quantify and to compare modifying effect of cellular/environmental factors in curing process of spheroids or tumors.

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Use of radioprotective drugs in radiotherapy is desirable to protect normal tissues. 2-mercaptopropionylglycine (MPG) has shown promising results in experimental radioprotection. In this report, a liposome drug delivery system for MPG has been used in Swiss albino mice exposed to 1 to 8 Gy whole body Gamma-irradiation to test whether or not this modality enhances the MPG afforded radio-protection. A statistically significant, dose dependent enhancement of protection by liposome encapsulated MPG (LEM) was observed. LEM, as compared to free MPG, improved the viabilities of spleen and bone marrow cells by factors between 1.11 and 2.23 for different doses of radiation.

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Interspecific and intraspecific hybrids were formed between mouse and Chinese hamster cell mutants hypersensitive to ionizing radiation and their radiosensitivities were examined. Chinese hamster cell mutants irs1, irs2 and irs3 and mouse mammary carcinoma cell mutants SX9 and SX10 have been found to belong to five different complementation groups. A radiosensitive mouse lymphoma cell line L5178Y-S has been demonstrated to be different from the X-ray sensitive mouse cell mutants M10 and LX830, both of which are derived from L5178Y cells, in their complementation groups. L5178Y-S is also distinct from SX9 and SX10.

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Plasmid pBR322 DNA (4363 base pairs) in aerobic aqueous solution was irradiated with ⁶⁰Co γ-radiation. The change of diffusion coefficients (D) of chemical species, rate constants (k) of radical-DNA interaction and solubilities of O₂ in water cannot be ignored when a temperature varies more than a few tens of centigrade. It is important to examine the variation of the yields of DNA strand breaks as a function of temperature in order to analyze the mechanisms of DNA strand breaks from the chemical point of view. Hence, we observed the change of the yield of strand breaks with temperatures between -20 and 42°C by agarose gel electrophoresis. We also observed the change of the yield of strand breaks with the concentration of OH scavenger (Tris) from 1 mmol dm^-3 to 100 mmol dm^-3 and summarized it with previous experiments. This summarization indicated that the order of the lifetime of OH radical in cellular environment is several nanosecond. This value is consistent with the measurement of the lifetime of 8.7 nanosecond for OH radical in mammalian cell (Roots, R. and Okada, S. (1975) Radiat. Res. 64, 306-320).

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More than a dozen cancer patients died in 1993 after treatment with antineoplastic derivatives of 5-fluorouracil and the antiherpes drug Sorivudine. This paper gives a short review of previous reports showing that killing of cells by 5-fluorouracil and other antitumor agents, including radiation at high doses, results from activation of apoptosis in the G2 phase. On the other hand, apoptosis of lymphocytes by radiation at low doses and treatment with other agents is known to occur in the G1 phase . The cells dying in the G1 or G2 phase could share the same final self-killing steps. For these common steps, I assume a mitotic catastrophe model, in which commitment to self-killing results from premature activation of the mitosis machinery, and propose a concept of a ‘G1/G2 death circuit'' for cells dying in the G1/G2 phase by short circuit to the M phase. Based on this model, reported modes of cell death, spontaneously occurring or after treatment with various agents, are classified by the phase of dying cells. The associations of incomplete apoptosis with production of chromosomal aberrations and prevention of tumorigenesis by complete apoptosis of carcingen-treated cells are discussed. A presumptive rule for differentiation of G1 apoptosis and G2 apoptosis is proposed.

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