Seventy-five percent of esophageal cancers are alcohol related, yet alcohol is not a carcinogen. Ethanol may promote carcinogenesis via increased free radical products during its metabolism, as indicated by data from this and other studies. Ethanol is oxidized to acetaldehyde by alcohol dehydrogenase, catalase and the microsomal ethanol oxidizing system (MEOS). Free radicals (FR) are released during the oxidation of ethanol by the MEOS. An increased formation of FR in tissues would increase their oxidative stress and may increase their susceptibility for developing chemically induced cancers. FR and some FR products can rapidly react with biological materials, i.e. lipids, proteins and nucleic acids, forming toxic products. This study focuses on the effects of FR and/or FR products on cancer promotion during alcohol metabolism. Eight groups of mice were fed nutritionally adequate diets supplemented with vitamin E and/or ethanol. Some groups of mice were also orally gavaged withN-nitrosomethylbenzylamine (NMBzA), an esophageal carcinogen. Following the feeding of the various diets for 22 weeks, livers and esophagi were removed and the FR burden in the liver measured by the presence of lipid peroxide products and the number of tumors in each esophagus determined. These studies indicate that a linear relationship exists between the increasing number of esophageal tumors and increasing levels of lipid peroxide products that are formed during FR activity. These results show that FR and/or FR products are the cancer promoters during ethanol metabolism, since diets supplemented with high levels of vitamin E, which inhibits ethanol-induced FR activity and the formation of FR products, suppress the promotion of cancer by ethanol Therefore, we conclude that FRs produced during ethanol metabolism and/or the products of FR activity are the cancer promoters attributed to ethanol.
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