Influence of effectors of prostaglandin metabolism on the toxicity induced by 7-hydroxymethyl-12-methylbenz(a)anthracene in cultured rat adrenal cells.
1. 7,12-Dimethylbenz(a)anthracene (DMBA) and 7-hydroxymethyl-12-methylbenz(a)anthracene (7-OHM-12-MBA), but not benzo(a)pyrene (BP), selectively produce necrosis in the two inner zones of the rat adrenal cortex and are toxic to cultured rat adrenocortical cells. 2. The toxicity induced by 7-OHM-12-MBA in the adrenocortical cells was partially prevented by the inhibitor of the cyclooxygenase activity of prostaglandin H synthetase, indomethacin. In contrast, indomethacin did not influence the effect of BP and DMBA on these cells. 3. Two other effectors of the prostaglandin metabolism, 5,8,11,14-eicosatetraynoic acid (ETYA) and nordihydroguaiaretic acid (NDGA), as well as the anti-inflammatory steroids cortisol and dexamethasone, partially protected against, whereas arachidonic acid and bradykinin exacerbated, the cytotoxicity induced by 7-OHM-12-MBA. 4. These results indicate that prostaglandin metabolism may be involved in the necrotic mechanism of 7-OHM-12-MBA in rat adrenal cortex.
Hallberg
E
E
Department of Biochemistry, Wallenberg Laboratory, University of Stockholm, Sweden.
Rydström
J
J
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity* / Q000031:analogs & derivatives; D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000633:toxicity; D001920:Bradykinin / Q000494:pharmacology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D006854:Hydrocortisone / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats
D001095:Arachidonic Acids; D011453:Prostaglandins; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; D001564:Benzo(a)pyrene; C018970:7-hydroxymethyl-12-methylbenz(a)anthracene; D015127:9,10-Dimethyl-1,2-benzanthracene; D009637:Masoprocol; D003907:Dexamethasone; D011451:Prostaglandin-Endoperoxide Synthases; D001920:Bradykinin; D006854:Hydrocortisone