Ethanol-mediated promotion of oral carcinogenesis in hamsters: association with lipid peroxidation.
Pouches of male Syrian Golden hamsters were painted with 1% 7,12-dimethylbenz[a]anthracene (DMBA) three times for one week. One week after DMBA treatment, hamsters were fed an ethanolic diet and continued on this diet until they were killed 22 and 35 weeks after the start of the experiment. Phospholipids, cholesterol, indexes of lipid peroxidation (malondialdehyde, diene and triene conjugates, lipid fluorescence), and the antioxidants glutathione and vitamin E were determined in the buccal mucosa, as was the incidence of tumors. At 22 weeks, the relative proportion of cholesterol to phospholipids in ethanol-consuming hamsters was significantly increased. At 35 weeks, most of the treatments showed a return of cholesterol vs. phospholipids toward that of untreated mucosa at 22 weeks. Ethanol consumption also increased the indexes of lipid peroxidation at 22 weeks; the largest increases occurred when ethanol use was combined with DMBA treatment. However, at 35 weeks such increases in lipid peroxidation had either returned to intermediate levels or were not different from the untreated controls at 22 weeks. Glutathione decreased in pouches of hamsters fed ethanol diets at 22 weeks, but at 35 weeks there was no appreciable difference. However, vitamin E increased significantly with ethanol consumption at 22 weeks, which increased further when combined with DMBA treatment, but at 35 weeks these values were intermediate. No tumors were seen at 22 weeks. At 35 weeks, DMBA-treated ethanol-fed hamsters had a significantly higher incidence of tumors, more multiple tumors per hamster with tumors, and more of the larger tumors than DMBA-treated control-fed hamsters. The results suggest that an increase in lipid peroxidation occurs with ethanol-related tumor promotion processes, but this lipid peroxidation declines when tumors appear to be preceded by increases in cholesterol relative to phospholipids and increases in vitamin E.
Nachiappan
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Department of Pharmacology and Toxicology, Arizona Health Sciences, University of Arizona, Tucson 85721.
Mufti
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Eskelson
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D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000287:Administration, Topical; D000818:Animals; D002610:Cheek; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D004357:Drug Synergism; D000431:Ethanol / Q000009:adverse effects*; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism; D009062:Mouth Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism
D010743:Phospholipids; D014810:Vitamin E; D000431:Ethanol; D015127:9,10-Dimethyl-1,2-benzanthracene; D002784:Cholesterol; D005978:Glutathione