Alcohol-stimulated promotion of tumors in the gastrointestinal tract.
Alcohol is a major risk factor for cancers of the upper gastrointestinal tract but the association with cancers of the large bowel is not as clearly established. In recent studies, we have provided experimental support for the associations in the esophagus and oral cavity. Our studies also indicate that the tumor promotion ability of ethanol is related to its ability to generate oxygen free radicals as measured by an increase in indices of lipid peroxidation. This increase in lipid peroxidation was evident in the liver as well as the tissues targeted by the site-specific carcinogens and promoted by ethanol. Studies in mice showed that the increased lipid peroxidation as well as tumor incidence was inhibited by the administration of vitamin E, the potent antioxidant. Determination of fatty acid profiles showed significant alterations when ethanol was used as a tumor promoter after treatment with the carcinogen. Ethanol as a promoter caused an increase in esophageal polyunsaturated fatty acids (PUFA). Ethanol promotion was also evident in increased arachidonate and an exaggeration in PUFA that are involved in eicosanoid production. Thus, these results suggest that ethanol-related promotion may be the result of excessive cell proliferation induced by disordered lipid and eicosanoid metabolism that may cause a selective outgrowth of the carcinogen-initiated cells. Supporting evidence for ethanol-induced hyper-regeneration is also reviewed.
Mufti
S I
SI
Department of Pharmacology and Toxicology, and the Arizona Cancer Center, University of Arizona Health Sciences Center, Tucson 85721, USA.
D000818:Animals; D006224:Cricetinae; D015777:Eicosanoids / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005770:Gastrointestinal Neoplasms / Q000139:chemically induced* / Q000209:etiology / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008647:Mesocricetus; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley
D015777:Eicosanoids; D005231:Fatty Acids, Unsaturated; D000431:Ethanol