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A series of micronucleus inducers were evaluated in the mouse bone marrow micronucleus test to determine if a 72-h sampling time enhances the sensitivity for detecting genotoxic agents. Male and female Swiss albino mice were dosed once with 7,12- dimethylbenz[a]anthracene, 6-mercaptopurine, benzo[a]pyrene, benzene, cyclophosphamide, 2-acetylaminofluorene, tubulazole, or mitomycin C. According to the EEC and OECD guidelines, the mice were killed at 24, 48 and 72 h after dosing. All test compounds induced an increase in the number of micronucleated polychromatic erythrocytes at 24 and/or 48 h. From the results obtained, it was evident that the 72-h sampling time does not enhance the sensitivity of the micronucleus test. The present data show that for screening purposes two sampling times at 24 and 48 h are sufficient to detect clastogens as well as aneugens. Although quantitative differences were found in sensitivity to micronucleus inducers between male and female mice, no qualitative differences were observed between the two sexes.

The eventual clastogenic properties of zinc chloride have been assessed as well in vitro as in vivo studies on mammalian somatic cells. For this purpose, human peripheral lymphocytes were treated in 48 or 72 hours cultures with 0, 20 or 200 micrograms zinc chloride, whereas C57Bl mice have received during one month a normal or poor calcium diet in combination or not with 0.5 g % of zinc. Chromosome analysis of treated human lymphocytes and of bone marrow cells of mice fed a poor dietary calcium supplemented with zinc has shown a significant increase in structural chromosome aberrations.

Whole human peripheral blood was exposed either acutely to 125 or 250 R X-rays or in fractions to 125+125 R X-rays at varying cell cycle times, namely, 0, 2, 4, 6, 8, 12, 16, 24, 30, 40 or 45 hours after culture initiation. Well spread metaphase chromosomes were examined for the following types of structural chromosome aberrations: dicentrics, rings, interstitial deletions, symetrical translocations, chromatid and chromosome fragments. Most noteworthy were found to be the polycentric + ring data. With acute radiation given at any of the times over the presynthetic period, the yields of these aberrations were consistently within the range of 17-20% for the 125 R dose and 66-73% for 250 R. For either acute dose given at later times, the aberration yields decreased to fall to 1% by the end of the synthetic period. With fractionated 125+125 R exposures the following rates were obtained: irradiation at 2 hr time in culture, 44.15%; 4 hr, 50.82%; 6 hr, 55.16%; 8 hr, 58,32% (peak rate): 12 hr, 55.48%. The downward trend persisted to the end of the presynthetic period and during the synthetic period. Statistical data treatment indicated acute and fractionated exposures to differ significantly in production of polycentric+ring yields, as well as in those of other aberration types and total breakage per cell. It may be concluded from our findings that the time course of repair processes is of an undulated pattern, with peak intensity within the first hours of the presynthetic period, a fall by 8 hr and a following renewed rise; repair was found to occur nearly to the end of the synthetic period.