Effects of indomethacin and arachidonic acid on sister chromatid exchange induction by styrene and styrene-7,8-oxide.
Styrene is converted into styrene-7,8-oxide in human lymphocyte cultures, in a reaction probably mediated by oxyhemoglobin. As a consequence, styrene induces sister-chromatid exchanges (SCEs) in whole-blood lymphocyte cultures without exogenous metabolic activation systems. Another metabolic pathway that could be involved in the metabolism of styrene is cooxidation by prostaglandin-endoperoxide synthase (PES). To study the role of PES in the metabolism of styrene, human whole-blood lymphocyte cultures were treated for the entire culture time of 72-h with styrene (0.5 and 1 mM) or styrene-7,8-oxide (50 and 100 microM), in the presence and absence of 75 or 150 microM indomethacin (an inhibitor of PES) and arachidonic acid (substrate of PES). Indomethacin potentiated SCE induction by both styrene and styrene-7,8-oxide; a slight but statistically significant enhancement (16-32%; p < 0.05-p < 0.001) was observed in all treatments with styrene and at 150 microM indomethacin in the case of styrene-7,8-oxide. At 150 microM, arachidonic acid induced a 15-20% suppression (p < 0.01) in SCE induction by both styrene (1 mM only) and styrene-7,8-oxide (100 microM only). Indomethacin or arachidonic acid did not alone influence the frequency of SCEs. The results suggest that PES acts as an inactivation route for styrene and styrene-7,8-oxide in human whole-blood lymphocyte cultures, possibly through PES-mediated binding to glutathione.
D000328:Adult; D016587:Antimutagenic Agents / Q000378:metabolism / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000378:metabolism / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D009153:Mutagens / Q000378:metabolism; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013343:Styrenes / Q000378:metabolism / Q000633:toxicity
D016587:Antimutagenic Agents; D016861:Cyclooxygenase Inhibitors; D004852:Epoxy Compounds; D009153:Mutagens; D013343:Styrenes; D016718:Arachidonic Acid; C013690:styrene oxide; D005978:Glutathione; D007213:Indomethacin