Metabolism and macromolecular binding of carcinogenic and noncarcinogenic metabolites of benzo(a)pyrene by hamster embryo cells.
نویسندگان
چکیده
The metabolism and macromolecular binding of four metabolites of benzo(a)pyrene in hamster embryo fibroblasts has been studied. Two noncarcinogenic phenolic derivatives, 3-hydroxybenz(a)pyrene and 9-hydroxybenzo(a)pyrene, are rapidly metabolized, primarily to their respective glucuronic acid conjugates and other H2O-soluble conjugates (78.4 to 80.8% of total radioactivity). Water-soluble conjugates were also formed from the carcinogenic phenol, 2-hydroxybenzo(a)pyrene, and from 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene, but in lower amounts (36.8 to 43.8% of total radioactivity. With each of the compounds, from 10 to 20% of the radioactivity was converted to ethyl acetate-soluble metabolites. The amount of unmetabolized 2-hydroxybenzo(a)pyrene recovered intracellularly was 20-fold higher than that recovered in incubations with the other phenols. Covalent binding to nuclear macromolecules was monitored after isopyknic separation. Binding of the three phenols tested was similar and was lower than the binding of benzo(a)pyrene to nuclear DNA, RNA, and protein. In contrast to the results with the monohydroxybenzo(a)pyrenes, high levels of covalent binding were observed with 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene; binding to DNA was 8-fold higher (315 pmol bound per mg DNA) than binding of benzo(a)pyrene to DNA.
منابع مشابه
Benzo(e)pyrene-induced alterations in the metabolic activation of benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene by hamster embryo cells.
Benzo(e)pyrene (BeP) is a cocarcinogen with benzo(a)pyrene (BaP) and an anticarcinogen with 7,12-dimethylbenz(a)anthracene (DMBA) in mouse skin initiation-promotion assays (Slaga, T.J., Jecker, L., Bracken, W.M. and Weeks C.E. Cancer Lett. 7: 51-59, 1979). We have investigated the effects of BeP on the metabolic activation of BaP and DMBA in early-passage cultures of Syrian hamster embryo cells...
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عنوان ژورنال:
- Cancer research
دوره 40 2 شماره
صفحات -
تاریخ انتشار 1980