Evaluation of Genotoxicity of 3-Amino-, 3-Acetylamino- and 3-Nitrobenzanthrone Using the Ames/Salmonella Assay and the Comet Assay
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概要
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3-Nitrobenzanthrone (3-NBA) is an extremely potent direct-acting bacterial mutagen that has been detected in diesel exhaust particles, airborne particles and so forth. Recently, 3-aminobenzanthrone (3-ABA) and 3-acetylaminobenzanthrone (3-AABA) were identified as metabolites of 3-NBA in mammalian cells. In this study, to clarify the genotoxicity of 3-ABA, 3-AABA and 3-NBA in vitro and in vivo, the mutagenicity and DNA-damaging activity of these chemicals were investigated by the Ames assay and by alkaline single gel electrophoresis (Comet assay), respectively. 3-ABA and 3-AABA were mutagenic toward four Salmonella typhimurium strains, i.e. TA98, TA100, YG1024 and YG1029, in the presence of a mammalian metabolic system (S9 mix). Both chemicals showed the highest mutagenicity toward YG1024, and induced 2180000 revertants/nmol of 3-ABA and 131000 revertants/nmol of 3-AABA. 3-NBA also showed mutagenicity toward these four strains with and without S9 mix, but the potencies of 3-NBA in these strains were decreased by the addition of S9 mix. In the presence of S9 mix, the mutagenic activities of 3-NBA in four strains were comparable to or lower than those on 3-ABA. 3-ABA, 3-AABA and 3-NBA produced statistically significant DNA damage, which was detected by an increase in the DNA tail moment, in vivo 3hr after intraperitoneal injection at 160mg/kg body weight. 3-ABA, 3-AABA and 3-NBA induced significant DNA damage in the liver, kidney, spleen and lung, spleen only, and liver, kidney, lung and bone marrow, respectively. At a lower dose (40mg/kg), 3-NBA produced significant DNA damage in the lung. These results indicate that 3-ABA, 3-AABA and 3-NBA are not only mutagenic in vitro in bacteria but also genotoxic in vivo in mouse.
- 公益社団法人日本薬学会の論文
- 2005-10-01
著者
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HIRAYAMA TERUHISA
Kyoto Pharmaceutical University
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Murahashi Tsuyoshi
Department of Public Health, Kyoto Pharmaceutical University
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Watanabe Tetsushi
Department Of Correlative Study In Physics And Chemisty Graduate School Of Integrated Basic Sciences
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Hirayama Teruhisa
Department Of Orthopaedic Surgery Asahikawa Medical College
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Tomiyama Tsuyoshi
Department Of Public Health Kyoto Pharmaceutical University
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Tomiyama Tsuyoshi
Department Of Electric Science Okayama University Of Science
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Nishijima Soichiro
Department of Public Health, Kyoto Pharmaceutical University
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Kanda Yuka
Department of Public Health, Kyoto Pharmaceutical University
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Murahashi Tsuyoshi
Kyoto Pharmaceutical University:(present Office)nihon Pharmaceutical University
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Hirayama Teruhisa
Kyoto College Of Pharmacy
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Nishijima Soichiro
Department Of Public Health Kyoto Pharmaceutical University
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Kanda Yuka
Department Of Public Health Kyoto Pharmaceutical University
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