Journal article
Multiple activation pathways of benzene leading to products with varying genotoxic characteristics
Environmental health perspectives, Vol.82, pp.81-89
07/1989
DOI: 10.1289/ehp.898281
PMID: 2676505
Abstract
Benzene and 13 potential metabolites were investigated for genotoxicity in Salmonella typhimurium and V79 Chinese hamster cells. In the presence of NADPH-fortified hepatic postmitochondrial fraction (S9 mix), benzene reverted his- S. typhimurium strains. The effect was strongest in strain TA1535. Among the potential metabolites, only the trans-1,2-dihydrodiol, in the presence of S9 mix, and the diol epoxides, in the presence and absence of S9 mix, proved mutagenic in this strain. The anti-diol epoxide was more potent than the syn-diastereomer. Both enantiomers of the anti-diastereomer showed similar activities. S9 mix did not appreciably affect the mutagenicity of the anti-diol epoxide. However, detoxification was observed when purified rat liver dihydrodiol dehydrogenase (EC 1.3.1.20) was used at concentrations comparable to that present in the liver. The (1S)-anti-diol epoxide was a much better substrate than the (1R)-enantiomer, as was true also for (1S)-versus (1R)-trans-1,2-dihydrodiol. The anti-diol epoxide reverted all six strains of S. typhimurium used and induced all four genotoxic effects studied in V79 cells (sister chromatid exchange greater than acquisition of 6-thioguanine resistance, acquisition of ouabain resistance, micronuclei). However, other potential benzene metabolites showed genotoxic effects in V79 cells, as well: sister chromatid exchange was induced by the syn-diol epoxide, 1,2,4-trihydroxybenzene, hydroquinone, catechol, and 1,2,3-trihydroxybenzene. Elevated frequencies of micronucleated cells were observed after treatment with hydroquinone, 1,2,4-trihydroxybenzene, catechol, phenol, 1,2,3-trihydroxybenzene, and quinone. Mutations to 6-thioguanine resistance were induced by quinone, hydroquinone, 1,2,4-trihydroxybenzene, catechol, and the trans-1,2-dihydrodiol.
Details
- Title: Subtitle
- Multiple activation pathways of benzene leading to products with varying genotoxic characteristics
- Creators
- Hansruedi Glatt - Department of Toxicology, University of Mainz, Federal Republic of GermanyRobert PadykulaGlenn A BerchtoldGabriele LudewigKarl L PlattFranz OeschJochen Klein
- Resource Type
- Journal article
- Publication Details
- Environmental health perspectives, Vol.82, pp.81-89
- Publisher
- United States
- DOI
- 10.1289/ehp.898281
- PMID
- 2676505
- ISSN
- 0091-6765
- eISSN
- 1552-9924
- Grant note
- CA09112 / NCI NIH HHS
- Language
- English
- Date published
- 07/1989
- Academic Unit
- Occupational and Environmental Health
- Record Identifier
- 9983997337602771
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