{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T04:19:11Z","timestamp":1771561151083,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,12,12]],"date-time":"2006-12-12T00:00:00Z","timestamp":1165881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2007,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Epidemiological studies indicate that there is a gender difference in the susceptibility to tobacco and environmental carcinogens, and this gender difference is suspected to result in a higher risk for lung cancer among women. However, the molecular mechanisms underlying this sexual dimorphism remain unclear. In the present study, we have evaluated the roles of CYP1A1 and dihydrodiol dehydrogenase (DDH) in the formation of benzo[<jats:italic>a<\/jats:italic>]pyrene (BaP) DNA adducts in various lung cancer cell lines. Among six lung cancer cell lines tested, higher adduct levels were observed in CL\u20103 and CL1\u20101 cells, which had relatively high expression of both CYP1A1 and DDH isoform 1 (DHH1). To determine whether a reduction in DDH expression changed the adduct levels, an siRNA was used to knock down DDH1 expression in CL\u20103 cells. The BaP adduct levels in siDDH\u2010CL\u20103 cells increased 1.4\u20132.2\u2010fold relative to that of the parental CL\u20103 cells. We also examined BaP\u2010like DNA adducts, and CYP1A1 and DDH1 expression by immunohistochemistry in 120 lung tumors. Detection of DNA adducts correlated with CYP1A1\u2010positive tumors (<jats:italic>P<\/jats:italic> = 0.023), but not with DDH1\u2010positive tumors. In addition, 28 of 33 tumors (85%) that were CYP1A1\u2010positive and DDH1\u2010negative contained detectable levels of DNA adducts, a proportion that was higher than for tumors from the other three categories of CYP1A1 and DDH1 expression (<jats:italic>P<\/jats:italic> = 0.012). Finally, a greater proportion of adduct\u2010positive tumors from females were CYP1A1\u2010positive\/DDH1\u2010negative (45.3%) than were tumors from males (27.3%). These results suggest that the reduction of DDH expression in lung tumors may contribute to an increase in DNA adduct levels, which may be partly responsible for the higher susceptibility of female lung cancer patients to DNA damage. Environ. Mol. Mutagen., 2007. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/em.20270","type":"journal-article","created":{"date-parts":[[2006,12,13]],"date-time":"2006-12-13T00:47:32Z","timestamp":1165970852000},"page":"14-21","source":"Crossref","is-referenced-by-count":4,"title":["A possible role for dihydrodiol dehydrogenase in the formation of benzo[<i>a<\/i>]pyrene\u2010DNA adducts in lung cancer cells and tumor 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