Induction of ouabain-resistant mutation and sister chromatid exchanges in Chinese hamster cells with chemical carcinogens mediated by human pulmonary macrophages.
Pulmonary macrophages (PAM) metabolically activated benzo[a]pyrene [B(a)P] and its proximate carcinogenic metabolite, (+/-)trans 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (7,8-diol), to ultimate mutagens that were detected in cocultivated Chinese hamster V79 cells. Increases in the frequency of ouabainresistant (O(r)) mutations and sister chromatid exchanges were found in V79 cells only when they were cocultivated with both PAM and the chemical procarcinogens. 7,8-Diol caused higher frequencies of both O(r) mutations and sister chromatid exchanges than did the parent compound, B(a)P. When metabolically activated by PAM the mean O(r) mutation frequency caused by B(a)P was 9 O(r) mutants/10(6) surviving V79 cells per 10(6) PAM and a 10-fold interindividual variation (range, 2-21) was found. The mean O(r) mutation frequency caused by 7,8-diol was 64 and a ninefold interindividual variation (range, 14-120) was found. In the absence of PAM, the O(r) mutation frequency in V79 cells was one or less O(r) mutant per 10(6) survivors. 7,8-Benzoflavone, an inhibitor of mixed function oxidases, reduced the frequencies of O(r) mutations and of sister chromatid exchanges in V79 cells caused by 7,8-diol and B(a)P. As expected 7,8-benzoflavone did not influence the frequency of O(r) mutations caused by one of the ultimate mutagens derived from B(a)P and 7,8-diol, (+/-)7beta, 8alpha-dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. These data are consistant with the hypothesis that PAM may play a role in the activation of environmental chemical procarcinogens.
D000230:Adenocarcinoma / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001164:Arteriovenous Fistula / Q000473:pathology; D001580:Benzopyrenes / Q000378:metabolism* / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002478:Cells, Cultured; D006259:Craniocerebral Trauma / Q000473:pathology; D006224:Cricetinae; D003412:Cricetulus; D003434:Crossing Over, Genetic / Q000187:drug effects*; D005260:Female; D006801:Humans; D008168:Lung / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009153:Mutagens; D009154:Mutation; D010042:Ouabain / Q000494:pharmacology; D011651:Pulmonary Artery; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D001580:Benzopyrenes; D009153:Mutagens; D010042:Ouabain