Effects of arachidonic acid and indomethacin on sister-chromatid exchange induction by polycyclic aromatic hydrocarbons in mammalian cell lines.
Arachidonic acid (AA), a prostaglandin precursor, significantly potentiated sister-chromatid exchange (SCE) induction in vitro by benzo[a]pyrene (BP) and 7,12-dimethylbenz[a]anthracene (DMBA) in the aryl hydrocarbon hydroxylase (AHH)-inducible human hepatoma C-HC-4 cells, and to a lesser extent in the non-inducible rat tumor AH66-B and R1 and Chinese hamster Don-6 cells, all of which were less sensitive to these compounds than C-HC-4 cells. Indomethacin (IM), an inhibitor of prostaglandin endoperoxide synthetase (PES), moderately suppressed SCE induction by BP or DMBA in AH66-B and R1 cells, but it exerted no such effect in C-HC-4 and Don-6 cells. In C-HC-4 cells, however, IM completely eliminated the potentiating effect of AA on SCE induction by both BP and DMBA. The above findings suggest that PES in prostaglandin biosynthesis may also be involved in the metabolic activation of polycyclic aromatic hydrocarbons to genotoxic forms capable of inducing SCEs, in addition to AHH system.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004357:Drug Synergism; D004790:Enzyme Induction; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000201:enzymology; D051381:Rats; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D001189:Aryl Hydrocarbon Hydroxylases; D007213:Indomethacin