Alcohol-associated generation of oxygen free radicals and tumor promotion.
We discuss evidence indicating how ethanol could generate oxygen free radicals. Recent use of techniques such as spin trapping and EPR spectroscopy have demonstrably confirmed that both acute and chronic alcohol use by laboratory animals would generate free radical intermediates. These radicals are of biological origin and presumably involve lipids. However, an exact identification of the intermediates produced has not been worked out with the currently available methodologies. Also not known is the mechanism whereby ethanol could initiate free radicals. The relationship between generation of free radicals and cell toxicity or carcinogenesis is also not understood. Using a variety of systems that included different species, strains and gender (male Sprague-Dawley and Fisher-344 rats, female C57BL/6 mice, male Syrian golden hamsters) and carcinogens (NMBZA, NNN, NNK, DMBA and LP-BM5 retrovirus) we have shown an association of lipid peroxidation with ethanol tumor promotionability. However, the process of tumor promotion in general is not very clear and the role played by ethanol in this process is still more unclear. Here we are reviewing evidence that could possibly be involved in such promotion processes.
Mufti
S I
SI
Department of Pharmacology, Arizona Cancer Center, University of Arizona, Tucson.
Eskelson
C D
CD
Odeleye
O E
OE
Nachiappan
V
V
D000818:Animals; D002273:Carcinogens / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects; D000431:Ethanol / Q000009:adverse effects* / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007502:Iron Chelating Agents / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D014968:Xanthine Dehydrogenase / Q000378:metabolism
D002273:Carcinogens; D005609:Free Radicals; D007502:Iron Chelating Agents; D000431:Ethanol; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D014968:Xanthine Dehydrogenase; D010100:Oxygen