Biomedical subjects
Publications and source records attributed to I Tobari.
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We have examined the chromosomal radiosensitivities of an ionizing-radiation-and MMS-sensitive mutant (M10), and a UV- and 4NQO-sensitive mutant (Q31), isolated from mouse lymphoma L5178Y cells, with regard to killing effects. In the first mitoses after 100 R gamma-irradiations, it was found that M10 cells were highly radiosensitive in terms of chromosomal aberrations accompanying longer mitotic delay (3 h); the frequencies of both chromatid-type and chromosome-type aberrations were, respectively, about 7 and 4 times higher than that of wild-type L5178Y cells. Furthermore, chromatid exchanges, particularly triradials, isochromatid breaks with sister union, and chromatid gaps and breaks were markedly enhanced at G1 phase of M10 cells. In contrast, the chromosomal radiosensitivity of Q31 cells after 100 R irradiation was similar to that of L5178Y cells. On the other hand, spontaneous aberration frequencies (overall breaks per cell) of M10 and Q31 cells were, respectively, 5.1 and 2.2 times higher than that of wild-type L5178Y cells. The chromosomal hypersensitivity to gamma-rays in M10 cells is discussed in the light of knowledge obtained from ataxia telangiectasia cells.
To obtain information on the relation between yield of chromosome aberrations and dose at low-dose levels, experiments were conducted with 5, 10, 20, 30 and 50 rad of 137Cs gamma-rays, on lymphocytes from man and crab-eating monkey (Macaca fascicularis). The dose-response relationship for dicentrics was obtained from the combined data of these low-dose experiments with those of our previous ones at high doses (100-400 rad). When the difference between observed yields and those expected from the linear-quadratic model were computed, the dose-response curve had a good fit for man, but not for the monkey. The linear regression lines between 0 and 30 rad were calculated, because the expected values of alpha/beta for man and monkey would be about 100 and 60 rad. The human data gave a satisfactory fit to a linear model, i.e., a linear increase in aberration frequency with dose, whereas this was not so for those of the monkey. Furthermore, there was some suggestive evidence for the existence of a plateau in dicentric yields between 10 and 30 rad for the monkey and between 20 and 30 rad for human lymphocytes, but more data would be needed to verify this suggestion, particularly for human lymphocytes.
The mutant mouse lymphoma cell M10, which is sensitive to methyl methanesulfonate and ionizing radiation, was compared with the parental L5178Y cells for mutation induction after gamma-irradiation. The rate of induced mutations to 6-thioguanine resistance in L5178Y cells was 2-3 X 10(-7) per R, as determined after exposures ranging from 25 to 500 R. The induced mutation frequency per unit dose per locus in M10 cells was about 4 times higher than that in L5178Y cells at the lower doses of exposure (25-75 R), but it declined sharply at the higher doses of gamma-rays (100-150 R). The rate of induced mutation per unit cell killing in M10 cells was nearly the same as that in L5178Y cells when they were compared at the levels of lower cell killing.
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The therapeutic effect of tiopronin on incipient senile cataracts was evaluated in 150 cases (275 eyes) by a double-blind study using nonactive placebo. A more favorable tendency to visual acuity was noted in the tiopronin than in the placebo group. The slit-lamp microscopic findings showed a statistically significant difference between the tiopronin and the placebo groups. Integrated judgement revealed tiopronin to be significantly effective as compared with the placebo. A side effect of fever with systemic eruption was observed in 1 case in the tiopronin group but disappeared completely when administration of the drug was discontinued.
A comparison has been made of dicentric yields in GO lymphocytes between man and crab-eating monkey, Macaca fascicularis, after acute and chronic gamma-irradiations. With acute irradiation (49.6 rad/min) there was no significant difference between them, but for the chronic irradiation (17.1 rad/h) a significant difference was observed between the species. When the dose-response relations were fitted to the linear-quadratic model (Y = alpha D + beta D2), the species-difference observed for chronic irradiation was almost entirely due to change in the value of beta. In addition, after chronic irradiation the beta-value for monkey was almost negligible, but that for man was significant. Post-irradiation incubation experiment showed that cells with dicentrics were partly eliminated during the course of chronic irradiation, because there were appreciable reductions of dicentric yields (ca. 25% for both man and monkey at 400 rad) together with mitotic indices (ca. 30% and 60% for man and monkey, respectively, at 400 rad). Accordingly, it would be reasonable to postulate that GO repair for dicentrics other than selection mechanism must play a major role in the effects of low dose rate. It can be further suggested that GO-repair capacity for chromosal damages leading to dicentrics may be different among different primate species.
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