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Metabolic activation of 6-hydroxymethylbenzo[a]-pyrene by sulfotransferases and its inactivation by glutathione transferases in rat liver
102 quercetin's UV spectrum at 330 nm with time (an increase in absorbance) was observed. This spectral change suggests an interaction between quercetin and SOD. Metallothionein also enhanced the mutagenicity of quercetin. However, in this case the UV spectrum at 330 nm showed very little change with time. This suggests that quercetin does not interact with metallothionein directly and metallothionein protects quercetin from degradation by trapping active oxygen. The arsenic compounds depressed the mutagenicity of quercetin in the presence of $9 mix. Consequently we have found that the mutagenicity of quercetin is enhanced by protection from active oxygen and activation with SOD. On the other hand it was suggested that the arsenic compounds depress the action of SOD on quercetin.
48 Okuda, H., N. Hasegawa and T. Watabe, Department of Hygienic Chemistry, Tokyo College of Pharmacy, 1432-1 Horinouchi, Hachioji-shi, Tokyo 192-03 (Japan)
Metabolic activation of 6-hydroxymethylbenzola]pyrene by sulfotransferases and its inactivation by glutathione transferases in rat liver The carcinogen 6-hydroxymethylbenzo[a]pyrene (6-HBP), which has been demonstrated to be metabolically formed from benzo[a]pyrene by 6-HBP synthetase in the rat lung, induced His + reverse mutation in S. typhimurium TA98 to a marked extent in the presence of a dialyzed rat liver cytosolic fraction ($105) fortified with 3'phosphoadenosine 5'-phosphosulfate (PAPS). The mutagenicity of 6-HBP in the presence of the PAPS-S105 system was not detectable when either boiled $105 was used for or PAPS was omitted from the activation system. A marked sex difference was observed in the sulfotransferase-mediated activation of 6-HBP in the rat liver, i.e., the mutagenicity of 6-HBP exerted by female $105 in the presence of PAPS was 7 times higher than that exerted by male $105. From the PAPS-female $105 system, the potent intrinsic mutagen 6-HBP sulfate was isolated by the TBA-extraction method and identified with a synthetic specimen. The intrinsic mutagenicity of 6-HBP sulfate was strongly delayed by the addition of $105 fortified with
glutathione (GSH). The mutagenicity of 6-HBP in the presence of the PAPS-S105 system was also strongly delayed by the addition of GSH. These results indicate that, in the rat liver, 6-HBP was conjugated by sulfotransferases to the reactive metabolite 6-HBP sulfate, which was readily scavenged to GSH conjugate by GSH transferases.
49 Ono, Y., I. Somiya and M. Kawamura, Department of Environmental and Sanitary Engineering, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto 606 (Japan)
Genotoxicity of the by-products produced in chlorination and ozonation processes The umu-test, which can detect the induction of DNA repair, was applied in order to analyze the genotoxicity of by-products of chlorination and ozonation. In this research work, the genotoxicities of 37 commercial chemicals which are expected to be involved in the by-products of chlorination and ozonation processes were checked and evaluated with the umu-test. The genotoxicities of the following organic halogenated compounds were clearly detected: without microsomal activation: rn-dichlorobenzene, 1,2,4-trichlorobenzene and bromoform; with microsomal activation: m-dichlorobenzene, dichloroacetic acid, trichloroacetic acid and chloral. Among the compounds which are expected to be produced by ozonation, formaldehyde and ionone showed positive genotoxicity without microsomal activation, and 5 compounds had positive genotoxicity with microsomal activation; they were formaldehyde, furfurol, carvone, glyoxal and acrolein. Some of the selected organic compounds, such as chloroform, were also identified as positively genotoxic, which have been reported not to be mutagenic in other bacterial assays. As a quantitative evaluation of genotoxicity of chemicals, the time of DNA repair of damaged spots by SOS genes (0-24 h) and the induction rate of the umu gene ( 0 - 0 . 2 0 / h ) were also experimentally investigated. 50 Osada, K. 1, y . Furukawa i, M. Komai 1, M. Kimura 2, K. Hishinuma 2, C. Saitoh 2, H.
48 Okuda, H., N. Hasegawa and T. Watabe, Department of Hygienic Chemistry, Tokyo College of Pharmacy, 1432-1 Horinouchi, Hachioji-shi, Tokyo 192-03 (Japan)
Metabolic activation of 6-hydroxymethylbenzola]pyrene by sulfotransferases and its inactivation by glutathione transferases in rat liver The carcinogen 6-hydroxymethylbenzo[a]pyrene (6-HBP), which has been demonstrated to be metabolically formed from benzo[a]pyrene by 6-HBP synthetase in the rat lung, induced His + reverse mutation in S. typhimurium TA98 to a marked extent in the presence of a dialyzed rat liver cytosolic fraction ($105) fortified with 3'phosphoadenosine 5'-phosphosulfate (PAPS). The mutagenicity of 6-HBP in the presence of the PAPS-S105 system was not detectable when either boiled $105 was used for or PAPS was omitted from the activation system. A marked sex difference was observed in the sulfotransferase-mediated activation of 6-HBP in the rat liver, i.e., the mutagenicity of 6-HBP exerted by female $105 in the presence of PAPS was 7 times higher than that exerted by male $105. From the PAPS-female $105 system, the potent intrinsic mutagen 6-HBP sulfate was isolated by the TBA-extraction method and identified with a synthetic specimen. The intrinsic mutagenicity of 6-HBP sulfate was strongly delayed by the addition of $105 fortified with
glutathione (GSH). The mutagenicity of 6-HBP in the presence of the PAPS-S105 system was also strongly delayed by the addition of GSH. These results indicate that, in the rat liver, 6-HBP was conjugated by sulfotransferases to the reactive metabolite 6-HBP sulfate, which was readily scavenged to GSH conjugate by GSH transferases.
49 Ono, Y., I. Somiya and M. Kawamura, Department of Environmental and Sanitary Engineering, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto 606 (Japan)
Genotoxicity of the by-products produced in chlorination and ozonation processes The umu-test, which can detect the induction of DNA repair, was applied in order to analyze the genotoxicity of by-products of chlorination and ozonation. In this research work, the genotoxicities of 37 commercial chemicals which are expected to be involved in the by-products of chlorination and ozonation processes were checked and evaluated with the umu-test. The genotoxicities of the following organic halogenated compounds were clearly detected: without microsomal activation: rn-dichlorobenzene, 1,2,4-trichlorobenzene and bromoform; with microsomal activation: m-dichlorobenzene, dichloroacetic acid, trichloroacetic acid and chloral. Among the compounds which are expected to be produced by ozonation, formaldehyde and ionone showed positive genotoxicity without microsomal activation, and 5 compounds had positive genotoxicity with microsomal activation; they were formaldehyde, furfurol, carvone, glyoxal and acrolein. Some of the selected organic compounds, such as chloroform, were also identified as positively genotoxic, which have been reported not to be mutagenic in other bacterial assays. As a quantitative evaluation of genotoxicity of chemicals, the time of DNA repair of damaged spots by SOS genes (0-24 h) and the induction rate of the umu gene ( 0 - 0 . 2 0 / h ) were also experimentally investigated. 50 Osada, K. 1, y . Furukawa i, M. Komai 1, M. Kimura 2, K. Hishinuma 2, C. Saitoh 2, H.