T. Guenthner, B. Jernström, S. Orrenius
May 1, 1980
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Influential Citations
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Quality indicators
Journal
Carcinogenesis
Abstract
The binding to DNA of products resulting from the further activation of trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene and 9-hydroxybenzo(a)pyrene was studied in several incubation systems. In a system containing purified DNA and rat liver microsomes, products of 9-hydroxybenzo(a)pyrene were the predominant binding species. In a system containing isolated rat hepatocytes, the total binding was much lower, and products of trans-7,8-dihydroxy-7, 8-dihydrobenzo(a)pyrene predominated. Both the total amounts and the ratios of the bound species were altered by the addition of various soluble nucleophiles to the incubation system. The binding of 9-hydroxybenzo(a)pyrene to both nuclear and purified DNA was decreased in the presence of "non-specific" protein in the incubate. A decrease in the binding of trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene to either purified or nuclear DNA was seen after the addition of active cytosol, but not with protein alone. Either denaturation of the cytosol, or depletion of glutathione by diethylmaleate treatment, partially negated this effect. We conclude that the binding of benzo(a)pyrene metabolites to DNA in the cell is decreased by soluble nucleophiles, and that this trapping of metabolites is selective. 9-Hydroxybenzo(a)pyrene metabolites are removed by non-specific protein binding, whereas removal of trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene metabolites requires higher affinity binding or enzymatic conjugation.