Genes and Environment
Online ISSN : 1880-7062
Print ISSN : 1880-7046
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29 巻 , 4 号
選択された号の論文の5件中1~5を表示しています
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REGULAR ARTICLES
  • Toshihiro Ohta
    29 巻 (2007) 4 号 p. 141-145
    公開日: 2007/12/04
    ジャーナル フリー
    DNA damages provoked by the six mutagens (furylframide, MX, 4-nitroquinoline N-oxide, sodium azide, 1-nitropyrene, and captan) used in the present study have been known to subject to the nucleotide excision repair system. Therefore, they induced base-substitution mutations much more efficiently in Salmonella typhimurium TA100 (hisG46, rfa, uvrB/pKM101), a strain deficient in nucleotide excision repair, than in TA1975P (hisG46, rfa/pKM101). Doses below undetectable level in the reverse mutation assay were selected as those that were apparently mutagenic to the repair-deficient strain TA100 but not to the repair-proficient strain TA1975P in this study. Then, the six mutagens were mixed at virtually non-mutagenic dose level of each and a possible combined mutagenic effect was investigated. A significant and reproducible increase in the number of revertants in TA1975P was observed with combined mutagens. The results suggest that DNA adduct formation at virtually non-mutagenic dose level was additive, with the total amount reflecting the mutagenicity.
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  • Yoshimitsu Oda, Tetsushi Watanabe, Hiroshi Yamazaki, Teruhisa Hirayama
    29 巻 (2007) 4 号 p. 146-152
    公開日: 2007/12/04
    ジャーナル フリー
    3-Nitrobenzanthrone (3-NBA) is a mutagenic and carcinogenic compound identified in diesel exhaust, airborne particulate matter, soil, and water. To address whether 3-NBA shows genotoxic effects through any metabolic activation pathway, we determined the genotoxicity of 3-NBA using the parental strain Salmonella enterica serovar Typhimurium (S. typhimurium) TA1535/pSK1002, nitroreductase (NR)-deficient strain NM1000, the O-acetyltransferase (O-AT)-deficient strain NM2000, bacterial O-AT-overexpressing strain NM2009, and bacterial NR- and O-AT-overexpressing strain NM3009 established in our laboratory. In order to further clarify the role of human cytochrome P450 (P450 or CYP) enzyme in the bioactivation of 3-NBA to genotoxic metabolites, umu tester strains S. typhimurium OY1022/1A1, OY1022/1A2, OY1022/1B1, and OY1022/3A4, which express four respective human cytochrome P450 enzymes, NADPH-cytochrome P450 reductases (NPR) and O-AT were established by introducing two plasmids into S. typhimurium TA1535NR/1,8-DNP (nitroreductase-deficient and resistant to 1,8-dinitropyrene, probably due to functional loss of O-AT), one carrying both P450 and reductase cDNA in a biocistronic construct under control of an IPTG-inducible double tac promoter and the other, pOA102, carrying O-AT and umuC'-'lacZ fusion genes. Induction of umuC gene expression could be monitored by measuring the cellular β-galactosidase activity produced by the umuC'-'lacZ fusion gene. Although the induction of umuC by 3-NBA was weak in TA1535/pSK1002, NM1000, and NM2000 strains, the induction was considerably potent in NM2009 and NM3009 strains. 3-NBA was also found to induce umuC gene expression in OY1022/1A1 and OY1022/3A4 strains and, to a lesser extent, OY1022/1A2 and OY1022/1B1 strains, at a much higher rate than the parental OY1022/pCW strain. Collectively, these results suggest nitroreduction and O-acetylation by bacterial NR and O-AT, respectively, and nitroreduction by human CYP1A1, 3A4, 1A2, and 1B1 and NPR could contribute to the genotoxic activation of 3-NBA to produce reactive metabolites.
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  • Satomi Kawaguchi, Takanori Nakamura, Gisho Honda, Yu F. Sasaki
    29 巻 (2007) 4 号 p. 153-158
    公開日: 2007/12/04
    ジャーナル フリー
    Although kojic acid is used as a cosmetic agent for skin whitening, information of its genotoxicity in in vitro assay is much complicated. In order to evaluate its genotoxic potentials in vitro, we conducted comet assay in regular and acellular versions, chromosome aberration assay, and TK mutation assay in human lymphoblastoid cells. Positive results were obtained in all of the comet, chromosome aberration, and TK mutation assays at almost identical concentration in both TK6 and WTK1 cells. In the acellular comet assay, kojic acid led to positive responses at pH12 and pH13, suggesting that it induced DNA single strand breaks (SSBs). In the TK mutation assay, kojic acid increased the fraction of normal growing but not slowly growing mutants, suggesting that observed gene mutations are due to point mutations within the TK locus but not gross structural changes that can form chromosome aberrations observable by a microscopy.
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SHORT COMMUNICATION
  • Izumi Ogawa, Satoshi Furukawa, Yoshinori Tanaka, Masayoshi Abe, Koji U ...
    29 巻 (2007) 4 号 p. 159-162
    公開日: 2007/12/04
    ジャーナル フリー
    In order to examine the utility of the in vivo Comet assay for evaluating genotoxicity in the uterus, we performed the Comet assay using rats' livers and uteri for four compounds: methyl methanesulfonate (MMS) and N-nitroso-N-diethylamine (DEN) as genotoxic compounds, indole-3-carbinol (I3C) and diethylstilbestrol (DES) as non-genotoxic compounds. Whether or not the sexual cycles affected the outcome of this assay was also investigated by treatment with saline and MMS. The results showed that there was no statistically significant difference in tail moment among the three sexual cycles either with the saline or MMS treatment. MMS and DEN, genotoxic carcinogens, induced a significant increase in the tail moment in both the uterus and liver. I3C, a non-genotoxic non-carcinogen, and DES, a non-genotoxic carcinogen, did not increase the tail moment significantly in either organ. We confirmed that the Comet assay using rat uteri can be used without considering the sexual cycle to assess in vivo genotoxicity in the uterus and help clarify the mechanism of carcinogenesis.
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