Micronucleus induction of metal compounds

264 strains without $9 mix. It has been reported that isocyanate generated by the O-acetylation of hydroxamic acid and the following Lossen rearrangement in the bacterial cells may be an ultimate mutagen. In this study, we examined whether the proposed mechanism is involved in the bacterial mutagenesis. No significant relationship between the decomposition rate to isocyanate and the mutagenicity was found in benzohydroxamic acid acyl derivatives or in para-substituted benzohydroxamic acid O-acetates. 2-Naphthohydroxamic acid (NHA) showed strong mutagenic activity toward S. typhimurium TA97, TA98, TA98NR, TA98 1,8-DNP6, and YG1024. Though NHA O-acetate (NHAOAc) induced 3-5 times more His + revertants than NHA in the plate incorporation test, it was found that NHA is more mutagenic than NHAOAc in a preincubation experiment. The bacterial metabolic disappearance of NHA and NHAOAc in the preincubation mixture (2 /zg each) was 6% and 18%, respectively. Pentachlorophenol and 2,4-dinitrophenol dose-dependently inhibited the mutagenesis by NHA, but not by NHAOAc. Hydro~lamine reduced the mutagenic activity of both NHA and NHAOAc. These results indicate that the ultimate mutagenie species of hydroxamic acid is an acyl derivative(s) other than O-acetate or isocyanatc. 38 Itoh, S., C. Hattori, Y. Matsuura and H. Shimada, Developmental Research Laboratories, Daiichi Pharmaceutical Co. Ltd., 1-16-13, Kitakasai, Edogawa-ku, Tokyo 134 (Japan)

Micronucleus induction of metal compounds Many heavy metal compounds are known to have mutagenic effects on the chromosomes of cultured mammalian cells and carcinogenicity has also been reported in some metals such as chromium, selenium, nickel, cobalt, arsenic, beryllium and lead. We studied the in vivo clastogenicity in the mouse micronucleus test of various metal compounds: chromium (K2CrO4, CrCla), manganese (MnCI 2, MnSO4), selenium (H, SeO a, Na2SeO4) and nickel (NiCl2, NiSO4).

Metal compounds were injected intraperitoneally once or twice to ddY male mice, then the polychromatic erythrocytes (PCEs) from the bone marrow were examined for micronucleus induction. Significant increases of micronucleated PCEs (MNPCEs) were observed only in the group of animals treated with K2CrO4 and HeSeO 3. In these compounds, the incidence of MNPCEs seemed to be reduced by double dosing. In addition, the incidences of MNPCEs were significantly decreased by pretreatment with Bi(NO3)3, a potent inducer of metaUothionein. These results suggest that the mechanism of micronucleus induction of the metal compounds involves a participation of metallothionein in the bone marrow.

39 lwakura, K. ~, H. Tamura ~, A. Matsumoto ~, Y. Yamashita ~, S. Ajimi e, S. Ogura 2, K. Kakimoto a, T. Matsumoto 2 and M. Hayashi 3, ~ Toxicological Laboratories, Nippon Shinyaku Co., Ltd., Kyoto 601, e Chemicals Inspection & Testing Institute, Japan, Chemical Biotesting Center, Hita 877, Oita and 3 Division of Mutagenesis, Biological Safety Research Center, National Institute of Hygienic Sciences, Tokyo 158 (Japan)

The micronucleus assay with peripheral blood reticulocytes by acridine orange supravital staining with 1-13-D-arabinofuranosylcytosine(ara-C) Previous studies with ara-C have indicated that the maximum frequencies of micronucleated reticulocytes (MNRETs) in peripheral blood lagged about 24 h behind those of micronucleated polychromatic erythrocytes (MNPCEs) in bone marrow. To more closely estimate the transition time from MNPCEs to MNRETs, we made precise time course experiments with 12-h intervals. The frequencies of MNPCEs peaked about 24 h and those of MNRETs about 36 h after i.p. treatment. It seems likely, therefore, that the transition time is closer to 12 h than 24 h. The concentrations of ara-C in plasma peaked at 0.5 h after i.p. treatment with 25 and 50 mg/kg and the chemical disappeared within 3 h. These results