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On the effect of cellular nucleophiles on the binding of metabolites of 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene and 9-hydroxybenzo(a)pyrene to nuclear DNA. 1980

T M Guenthner, and B Jernström, and S Orrenius

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.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D002467 Cell Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed) Cell Nuclei,Nuclei, Cell,Nucleus, Cell
D003853 Deoxyribonucleosides A purine or pyrimidine base bonded to DEOXYRIBOSE.
D004101 Dihydroxydihydrobenzopyrenes Benzopyrenes saturated in any two adjacent positions and substituted with two hydroxyl groups in any position. The majority of these compounds have carcinogenic or mutagenic activity. Benzopyrene Dihydrodiols,Dihydrobenzopyrene Diols,Dihydrodiolbenzopyrenes,Dihydrodiols, Benzopyrene,Diols, Dihydrobenzopyrene
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D006868 Hydrolysis The process of cleaving a chemical compound by the addition of a molecule of water.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001580 Benzopyrenes A class of chemicals that contain an anthracene ring with a naphthalene ring attached to it. Benzpyrene
D013347 Subcellular Fractions Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163) Fraction, Subcellular,Fractions, Subcellular,Subcellular Fraction

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