Metabolismof 6-Methylbenz[a]anthraceneby Rat LiverMicrosomesand Mutagenicityof Metabolites1
نویسندگان
چکیده
6-Methylbenz|a (anthracene (6-MBA) is metabolized by rat liver microsomes to form 3-hydroxy-6-MBA, 4-hydroxy-6-MBA, 5hydroxy-6-MBA, 6-MBA frans-3,4-, 5,6-, 8,9-, and 10,11-dihydrodiols, and 4-hydroxy-6-MBA frans-10,11-dihydrodiol as the identifiable metabolites. 6-Hydroxymethylbenz[a]anthracene and its phenolic and dihydrodiol metabolites are also formed. The unique metabolites identified in 6-MBA metabolism are 6-MBA frans-5,6-dihydrodiol and 4-hydroxy-6-MBA frans-10,11 -dihydro diol. Metabolites were isolated by reversed-phase and normalphase high-performance liquid chromatographies and identified by UV-visible absorption, mass, and proton nuclear magnetic resonance spectral analyses. Metabolites formed by low and high concentrations of liver microsomal enzymes from untreated, phenobarbital-treated, and 3-methylcholanthrene-treated male Sprague-Dawley rats were quantified by using [3H]6-MBA, with the tritium labeled at the methyl carbon, and liquid scintillation counting of fractions collected from reversed-phase high-per formance liquid chromatography. Metabolic formations of 6hydroxymethylbenz[a]anthracene, 6-MBA frans-dihydrodiols, and 4-hydroxy-6-MBA frans-10,11-dihydrodiol are highly de pendent on the contents of cytochrome P-450 isozymes present in liver microsomes. The relative mutagenic activities of metab olites toward Salmonella typhimurium TA100 are: 6-MBA frans3,4-dihydrodiol > 6-MBA frans-8,9-dihydrodiol > 6-MBA > 6MBA frans-10,11 -dihydrodiol > 4-hydroxy-6-MBA = 4-hydroxy6-MBA frans-10,11-dihydrodiol. The relatively high mutagenic activities of 6-MBA frans-3,4-dihydrodiol and 6-MBA frans-8,9dihydrodiol suggest that both 6-MBA frans-3,4-dihydrodiol 1,2epoxide(s) and 6-MBA frans-8,9-dihydrodiol 10,11-epoxide(s) may be the major metabolites which contribute to the carcino genic properties of 6-MBA.
منابع مشابه
The metabolism of 7- and 12-methylbenz[a]anthracene and their derivatives.
1. 7- and 12-Methylbenz[a]anthracene were converted by rat-liver homogenates into the corresponding hydroxymethyl derivatives, products that are probably the 8,9-dihydro-8,9-dihydroxy and the 5,6-dihydro-5,6-dihydroxy derivatives, and a number of phenolic products. 2. Both hydrocarbons were converted into glutathione conjugates; that from 7-methylbenz[a]anthracene was also formed, together with...
متن کاملComparison of the Products of the Reaction of 7-Methylbenz- [a]anthracene 5,6-Oxide and RNA, with Those Formed in 7-Methylbenz[a]anthracene-treated Cells
RNA was isolated by a phenol extraction method from mouse embryo cells treated in culture with either [G-~H]-7 methylbenz[a]anthracene or [G-:'H]-7-methylbenz[a]anthracene 5,6-oxide (the K-region epoxide). The RNA was degraded to ribonucleosides, mixed with ultraviolet-absorbing quantit ies of the epoxide ribonucleoside products isolated from RNA that had reacted with 7-methylbenz[a]anthracene ...
متن کاملStudies on the Formation of Hydrocarbon-Deoxyribonucleoside Products by the Binding of Derivatives of 7-Methylbenz[a]anthracene to DN A in Aqueous Solution and in Mouse Embryo Cells in Culturel
DNA was isolated from mouse embryo cell cultures that had been treated with 7-methylben/[fl]anthracene-3H and subsequently degraded with enzymes to deoxyribonucleosides that were chromatographed on a Sephadex LH-20 column. The resultant hydrocarbon-deoxyribonucleoside products were not present in similar enzyme digests of DNA that had been reacted in aqueous solution with either 7-bromomethylbe...
متن کاملComparison of the products of the reaction of 7-methylbenz(a)anthracene 5,6-oxide and RNA, with those formed in 7-methylbenz(a)anthracene-treated cells.
RNA was isolated by a phenol extraction method from mouse embryo cells treated in culture with either [G-3H]-7-methylbenz(a)anthracene or [G-3H]-7-methylbenz(a)anthracene 5,6-oxide (the K-region epoxide). The RNA was degraded to ribonucleosides, mixed with ultraviolet-absorbing quantities of the epoxide ribonucleoside products isolated from RNA that had reacted with 7-methylbenz(a)anthracene 5,...
متن کاملPhotochemical Reaction of 7,12-Dimethylbenz[a]anthracene (DMBA) and Formation of DNA Covalent Adducts
DMBA, 7,12-dimethylbenz[a]anthracene, is a widely studied polycyclic aromatic hydrocarbon that has long been recognized as a probable human carcinogen. It has been found that DMBA is phototoxic in bacteria as well as in animal or human cells and photomutagenic in Salmonella typhimurium strain TA102. This article tempts to explain the photochemistry and photomutagenicity mechanism. Light irradia...
متن کامل