{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,6]],"date-time":"2025-04-06T18:43:02Z","timestamp":1743964982951},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,7,20]],"date-time":"2006-07-20T00:00:00Z","timestamp":1153353600000},"content-version":"vor","delay-in-days":4187,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[1995,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>DNA repair\u2013deficient (xeroderma pigmentosum group A (XPA)) and DNA repair\u2010proficient (normal) human skin fibroblasts were genetically engineered by transformation with a controllable human cytochrome P450 (CYP)1A1 expression vector. Induction of CYP1A1 enabled these cells to metabolize (\u00b1)\u2010benzo[<jats:italic>a<\/jats:italic>]pyrene\u2010<jats:italic>trans<\/jats:italic>\u20107,8\u2010dihydrodiol (BPD) into a potent cytotoxicant and mutagen. The XPA cells were more susceptible than the normal cells to the cytotoxic effects of both CYP1A1\u2010metabolized BPD and exogenously supplied (\u00b1)\u2010<jats:italic>anti<\/jats:italic>benzo[<jats:italic>a<\/jats:italic>]pyrene\u2010<jats:italic>trans<\/jats:italic>\u20107,8\u2010dihydrodiol\u20109, 10\u2010epoxide (BPDE). Furthermore, the differential cytotoxicity between XPA and normal cells induced by CYP1A1\u2010metabolized BPD was 8.4\u2010fold greater than that induced by exogenously supplied BPDE. The two cell lines had similar CYP1A1 activities, suggesting that a difference in metabolic potential was not the cause of the differential response to BPD. At comparable cytotoxicity in both XPA and normal cells, BPD treatment induced more mutants and more DNA adducts than BPDE treatment did. At similar levels of DNA adducts in XPA cells, the levels of cytotoxicity induced by CYP1A1\u2010metabolized BPD and exogenously supplied BPDE were similar, but CYP1A1\u2010metabolized BPD induced a threefold higher hypoxanthine phosphoribosyltransferase mutation frequency. In contrast, at similar levels of adducts in CYP1A1\u2010expressing normal cells, BPD induced less cytotoxicity and a lower mutation frequency. DNA adducts were identified and quantified by <jats:sup>32<\/jats:sup>P\u2010postlabeling analyses. The principal adduct formed by both CYP1A1\u2010metabolized BPD and exogenously supplied BPDE was 10\u2010\u03b2\u2010(deoxyguanosin\u2010N<jats:sup>2<\/jats:sup>\u2010yl)\u20107\u03b2,8\u03b1,9\u03b1\u2010trihydroxy\u20107,8,9,10\u2010tetrahydrobenzo[<jats:italic>a<\/jats:italic>]pyrene, indicating that the differential effects of BPD\u2010 and BPDE\u2010induced adducts were not due to a difference in the types of adducts formed. The results of these studies suggest that CYP1A1\u2010metabolized BPD may form adducts preferentially in transcriptionally active genes or that the intracellular concentration of BPDE may influence the balance between cytotoxicity and mutagenicity (or both). \u00a9 1995 Wiley\u2010Liss Inc.<\/jats:p>","DOI":"10.1002\/mc.2940120206","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T21:00:36Z","timestamp":1172091636000},"page":"91-102","source":"Crossref","is-referenced-by-count":11,"title":["Differential mutagenicity and cytotoxicity of (\u00b1)\u2010benzo[<i>a<\/i>]pyrene\u2010<i>trans<\/i>\u20107,8\u2010dihydrodiol and (\u00b1)\u2010<i>anti<\/i>\u2010benzo[<i>a<\/i>]pyrene\u2010<i>trans<\/i>\u20107,8\u2010dihydrodiol\u20109, 10\u2010epoxide in genetically engineered human fibroblasts"],"prefix":"10.1002","volume":"12","author":[{"given":"Taihao","family":"Quan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John J.","family":"Reiners","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra J.","family":"Culp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Richter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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