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The genotoxicity of organotin compounds with bacterial assays
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YGI042, which have high levels ef both nitroreductase and O-acetyltransferase activities. To construct these strains, we subcloned both the nitroreductase gene and the O-acetyltransferase gene of S. typhimurium into a derivative of pACYC184 plasmid, which has a kanamycin-resistant gene instead of a chloramphenicol-resistant gene. The resulting plasmid, pYG233, was introduced into TA98 and TA100. The transformants, YGI041 and YGI042, showed almost the same nitrofurazone reductase activities as did YG1021 and YG1026, and also showed 3-5 times higher O-acetyltransferase activities than did YG1024 and YG1029. Twenty-nine mutagens with different structures were tested using these new strains and their sensitivities were compared with those of previously established strains as well as of TA98 and TA100. YG1041 and YG1042 had much higher sensitivities to some nitro-containing chemicals such as 2-nitrofluorene, 1-nitropyrene and p-nitrophenetole than did the other strains while they showed similar levels of sensitivity to aromatic amino compounds as did VGI024 and YGI029. These results indiczte that the new strains permit the efficient detection of the mutagenicity of environmental nitroarenes, 18 Hamasaki, T., T. Sato, H. Nagase, H. Kito, N. Noiri and A. Haga, Department of Public Health, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu City 502 (Japan)
The genotoxicity of organotin compounds with bacterial assays Recently, the environmental pollution by organotin compounds has become a serious problem, but detailed studies on the genotoxicity of various organotin compounds with bacterial assays have not been reported. The genotoxicity of 14 organotin compounds (butyltins, phenyitins, methyltins) and inorganic tin, which are known to exist in the environment, was studied with the SOS-chromotest. the rec-assay and the IMF test (S. typhimurium TA100). With the SOS-chromotest, a significant increase of 0-galactosidase activity from control (DMSO) (p < 0.05) was ob-
served for monobutyltin oxide, butyltin trichloride and dibutyl dichloride. Especially, butyltin dichloride showed high SOS-inducing potency at a low amount (0.05/~g/ml). With the rec-assay, dibutyltin dichloride, tributyltin chloride, TBTO, dimethyltin dichloride and trimethyltin chloride showed significant DNA damage. It is noteworthy that tributyltin chloride was appraised to be a DNA damager at 10/~g/disk. Moreover, it was proved that monobutyltin oxide, butyltin trichloride, dibutyltin dichloride, tributyltin chloride, TBTO and dimethyltin dichloride had significant mutagenicity by the IMF test. The IMF values of these compounds were in the order of 10 -6 to 10 -5 . The existence and mobility in the environment of several organotin compounds which gave rise to genotoxicity (e.g., butyltins, methyltins) by our experiments deserve attention.
19 Hata, M., A. Sugiyama and K. Yoshikawa, Toxicology Laboratory, Life Science Research Sector, Research Center, Mitsubishi Kasei Co., 1000 Kamoshida-cho, Midori-ku, Yokohama, Kanagawa 227 (Japan)
Formation of 8-hydroxydeoxyguanosine (8-OHdG) with metal compounds in vitro It is welbknown that 8-hydroxydeoxyguanosine (8-OH-dO) is generated by the action of oxygen radicabforming agents on DNA, and that the formation of this 8-OH-dG leads to mutations. The purpose of this study was to examine 8-OHdO yields after in vitro treatment with 13 metal compounds in the presence or absence of H202. Seven of the metal compounds used produced 8-OH-dG. The metal compounds investigated were CdCI 2, CoC! 2, CrCI3, K2Cr20 . CuCi2, FeCl 2, FeCl 3, MnCl 2, NiCI 2, Ni(OH) 2, PbCl 2, SnCl 2 and ZnCl 2. Calf thymus DNA (500 ~tg/ml) was incubated with each metal compound for 30 rain at 37°C with or without 100 ~tM H202.After incubation, isolated DNA samples were enzymatically hydrolysed and measured for 8-OH-dG yield by HPLC-ECD. In the presence of H202, the extent of 8-OH-dG formation (molecules/105 dG) showed the following order: FeCl2> FeCl3>
YGI042, which have high levels ef both nitroreductase and O-acetyltransferase activities. To construct these strains, we subcloned both the nitroreductase gene and the O-acetyltransferase gene of S. typhimurium into a derivative of pACYC184 plasmid, which has a kanamycin-resistant gene instead of a chloramphenicol-resistant gene. The resulting plasmid, pYG233, was introduced into TA98 and TA100. The transformants, YGI041 and YGI042, showed almost the same nitrofurazone reductase activities as did YG1021 and YG1026, and also showed 3-5 times higher O-acetyltransferase activities than did YG1024 and YG1029. Twenty-nine mutagens with different structures were tested using these new strains and their sensitivities were compared with those of previously established strains as well as of TA98 and TA100. YG1041 and YG1042 had much higher sensitivities to some nitro-containing chemicals such as 2-nitrofluorene, 1-nitropyrene and p-nitrophenetole than did the other strains while they showed similar levels of sensitivity to aromatic amino compounds as did VGI024 and YGI029. These results indiczte that the new strains permit the efficient detection of the mutagenicity of environmental nitroarenes, 18 Hamasaki, T., T. Sato, H. Nagase, H. Kito, N. Noiri and A. Haga, Department of Public Health, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu City 502 (Japan)
The genotoxicity of organotin compounds with bacterial assays Recently, the environmental pollution by organotin compounds has become a serious problem, but detailed studies on the genotoxicity of various organotin compounds with bacterial assays have not been reported. The genotoxicity of 14 organotin compounds (butyltins, phenyitins, methyltins) and inorganic tin, which are known to exist in the environment, was studied with the SOS-chromotest. the rec-assay and the IMF test (S. typhimurium TA100). With the SOS-chromotest, a significant increase of 0-galactosidase activity from control (DMSO) (p < 0.05) was ob-
served for monobutyltin oxide, butyltin trichloride and dibutyl dichloride. Especially, butyltin dichloride showed high SOS-inducing potency at a low amount (0.05/~g/ml). With the rec-assay, dibutyltin dichloride, tributyltin chloride, TBTO, dimethyltin dichloride and trimethyltin chloride showed significant DNA damage. It is noteworthy that tributyltin chloride was appraised to be a DNA damager at 10/~g/disk. Moreover, it was proved that monobutyltin oxide, butyltin trichloride, dibutyltin dichloride, tributyltin chloride, TBTO and dimethyltin dichloride had significant mutagenicity by the IMF test. The IMF values of these compounds were in the order of 10 -6 to 10 -5 . The existence and mobility in the environment of several organotin compounds which gave rise to genotoxicity (e.g., butyltins, methyltins) by our experiments deserve attention.
19 Hata, M., A. Sugiyama and K. Yoshikawa, Toxicology Laboratory, Life Science Research Sector, Research Center, Mitsubishi Kasei Co., 1000 Kamoshida-cho, Midori-ku, Yokohama, Kanagawa 227 (Japan)
Formation of 8-hydroxydeoxyguanosine (8-OHdG) with metal compounds in vitro It is welbknown that 8-hydroxydeoxyguanosine (8-OH-dO) is generated by the action of oxygen radicabforming agents on DNA, and that the formation of this 8-OH-dG leads to mutations. The purpose of this study was to examine 8-OHdO yields after in vitro treatment with 13 metal compounds in the presence or absence of H202. Seven of the metal compounds used produced 8-OH-dG. The metal compounds investigated were CdCI 2, CoC! 2, CrCI3, K2Cr20 . CuCi2, FeCl 2, FeCl 3, MnCl 2, NiCI 2, Ni(OH) 2, PbCl 2, SnCl 2 and ZnCl 2. Calf thymus DNA (500 ~tg/ml) was incubated with each metal compound for 30 rain at 37°C with or without 100 ~tM H202.After incubation, isolated DNA samples were enzymatically hydrolysed and measured for 8-OH-dG yield by HPLC-ECD. In the presence of H202, the extent of 8-OH-dG formation (molecules/105 dG) showed the following order: FeCl2> FeCl3>