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Species variance in the metabolic activation of polycyclic hydrocarbons

Conference ·
OSTI ID:6389192
Polycyclic hydrocarbons are metabolized to a series of oxygenated derivatives consisting of dihydrodiols, phenols, and quinones. A comparison of cell-free and intact cell systems show considerable variation for benzo(a)pyrene metabolism depending upon the presence or absence of cytoplasmic transferases for conjugation of these hydroxylated derivatives. Comparative metabolism studies, including microsomes and intact cells from rat, mouse, hamster, and humans yield identical qualitative metabolite profiles with significant quantitative variation. Macromolecular studies of benzo(a)pyrene diol-epoxides in hamster cells show specific binding of 7,8-diol-9,10-epoxide to DNA and 9,10-diol-7,8-epoxide to selected nuclear proteins. Comparative analysis of SDS-polyacrylamide gel electrophoresis suggest a unique specificity for regions of the benzo(a)pyrene molecule at the nuclear level. In addition, studies of carcinogenic 2-hydroxy-benzo(a)pyrene in cell culture were conducted. A diphenol was isolated and characterized as the major product in embryonic fibroblasts. A second minor metabolite was observed. The ratio of these two metabolites was reversed for epidermal cells.
Research Organization:
Oak Ridge National Lab., TN (USA); Tennessee Univ., Oak Ridge (USA). Graduate School of Biomedical Sciences
DOE Contract Number:
W-7405-ENG-26
OSTI ID:
6389192
Report Number(s):
CONF-810247-2; ON: DE81023229
Country of Publication:
United States
Language:
English