Free Radicals Generated in Ethanol Metabolism May Be Responsible for Tumor Promoting Effects of Ethanol

  • Siraj I. Mufti
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 283)


Chronic alcohol consumption is considered a major risk factor for human cancers [for example, Hakulinen et al., 1974; Breslow and Enstrom, 1974; Feldman et al., 1975; Williams and Horm, 1977; Schottenfeld, 1979; Kono and Ikeda, 1979; Tuyns, 1979; Doll and Peto, 1981]. The main sites associated with alcohol-related cancers are the oral cavity, esophagus and liver [Hakulinen et al., 1974; Breslow and Enstrom, 1974; Feldman et al., 1975; Kono and Ikeda, 1979; Rothman et al., 1980; Tuyns, 1982; Vassallo et al., 1985] and 75% of esophageal cancers and 36% of hepatic cancers in the U.S.A. are attributable to excessive alcohol consumption [Rothman et al., 1980]. Despite the strong epidemiologic evidence, however, experimental evidence for the association is not clear and often contradictory results have been obtained [Schmahl et al., 1965; Gibel, 1967; Schmahl, 1976; Griciute et al., 1982; Gabrial et al., 1982; Habs and Schmahl, 1981; Teschke et al., 1983; McCoy et al., 1986]. In order to clarify the role of ethanol, recently we carried out studies where ethanol was administered either during the initiation of carcinogenesis or later as a tumor promoter after initiation with the carcinogen was completed [Mufti et al., 1989]. Our results showed that ethanol increased esophageal tumor incidence only when administered after treatment with esophagus specific carcinogen, N-nitrosomethylbenzylamine (NMBzA) was completed. However, in studies of carcinogenesis induced by N-nitrosodiethylamine (NDEA), reported in another article in these proceedings, we did not find an increase either in liver tumors or gamma glutamyltranspeptidase-altered hepatic islands that could be attributed to the tumor promoting effects of ethanol [Mufti and Sipes, 1990]. This paper is a preliminary report of our investigations into the mechanisms of alcohol-related carcinogenesis that could be used to explain the contradictory effects of ethanol obtained with NMBzA- and NDEA-induced carcinogenesis.


Esophageal Cancer Ethanol Consumption Excessive Alcohol Consumption Mixed Function Oxidase Chronic Alcohol Consumption 
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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Siraj I. Mufti
    • 1
  1. 1.Department of Pharmacology and ToxicologyThe University of Arizona Health Sciences CenterTucsonUSA

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