Induction of monoamine oxidase B by 17 beta-estradiol in the hamster kidney preceding carcinogenesis.
Estrogen-induced kidney tumorigenesis in the male Syrian hamster has been postulated to be mediated by free radicals generated by metabolic redox cycling of catecholestrogen intermediates. This tissue and other rodent tissues in which tumors develop in response to estrogen treatment have been shown to contain high levels of the catecholamine norepinephrine. In this study, we have thus examined the hypothesis that an additional source of free radicals may be hydrogen peroxide formed by the monoamine oxidase (MAO)-catalyzed deamination of catecholamines. We have studied the effect of 17beta-estradiol (25-mg pellet, sc) on MAO activity in the hamster kidney (a target organ) and in the hamster liver and the rat kidney and liver, organs which do not develop tumors under these conditions. 17beta-Estradiol treatment for 2 weeks significantly increased (P < 0.01) MAO activity in the hamster kidney (76.7 +/- 10.0 and 113.0 +/- 10.8% over controls for the substrates tyramine and kynuramine, respectively). MAO activity remained elevated after 4 weeks of 17beta-estradiol treatment. No significant changes were observed in the MAO activity of hamster liver or rat kidney and liver. The addition of Tamoxifen to 17beta-estradiol restored control levels of renal MAO activity. The use of selective MAO A and MAO B inhibitors (clorgyline and deprenyl, respectively) identified the B form as the major component of hamster kidney MAO activity and its hormonal regulation. In conclusion, the estrogen receptor-mediated activation of MAO in conjunction with high catecholamine concentrations in the hamster kidney as previously reported may significantly increase the production of hydrogen peroxide and hydroxyl radicals which are postulated to contribute to tumor initiation.
Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, Texas, 77555-1031, USA.
S F
SF
Sarabia
J G
JG
Liehr
D000818:Animals; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006224:Cricetinae; D004790:Enzyme Induction / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D008995:Monoamine Oxidase / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000494:pharmacology
D002273:Carcinogens; D004965:Estrogen Antagonists; D013629:Tamoxifen; D004958:Estradiol; D008995:Monoamine Oxidase