Influence of effectors of prostaglandin metabolism on the toxicity induced by 7-hydroxymethyl-12-methylbenz(a)anthracene in cultured rat adrenal cells.

Abstract

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.

• Authors: E Hallberg, J Rydström
• Journal: Xenobiotica; the fate of foreign compounds in biological systems (Xenobiotica) Vol. 20 Issue 12 Pg. 1311-8 (Dec 1990) ISSN: 0049-8254 [Print] England
• PMID: 2127491 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Arachidonic Acids
• Prostaglandins
• 5,8,11,14-Eicosatetraynoic Acid
• Arachidonic Acid
• Benzo(a)pyrene
• 7-hydroxymethyl-12-methylbenz(a)anthracene
• 9,10-Dimethyl-1,2-benzanthracene
• Masoprocol
• Dexamethasone
• Prostaglandin-Endoperoxide Synthases
• Bradykinin
• Hydrocortisone

Topics

• 5,8,11,14-Eicosatetraynoic Acid (pharmacology)
• 9,10-Dimethyl-1,2-benzanthracene (toxicity)
• Adrenal Cortex (cytology, drug effects, metabolism)
• Animals
• Arachidonic Acid
• Arachidonic Acids (pharmacology)
• Benzo(a)pyrene (toxicity)
• Bradykinin (pharmacology)
• Cells, Cultured
• Dexamethasone (pharmacology)
• Drug Synergism
• Hydrocortisone (pharmacology)
• Masoprocol (pharmacology)
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Prostaglandins (metabolism)
• Rats