The effect of the chronic administration of liver carcinogens and tumor promoters on the hepatic levels of S-adenosylmethionine in rats

Abstract

Chemical carcinogenesis has been shown to occur in 2 or more stages viz. 1. initiation an early, rapid and generally irreversible change commonly thought to be the consequence of an attack by electrophilic metabolites of chemical carcinogens on DNA and 2. promotion, a slower process commonly associated with increased cell proliferation, which permits the development of an initiated cell into a tumor. Peraino et al. (1975), using phenobarbital and DDT as promoters, have extended to rat liver the concept of a 2-stage mechanism of carcinogenesis. Considerable indirect evidence indicates that a physiological methyl insufficiency may contribute to the promotion stage of hepatocarcinogenesis. The major observations leading to the development of this hypothesis may be summarized as follows: 1. The chronic administration of choline-deficient diets led to the production of hepatocellular carcinomas in rats (Salmon and Copeland, 1954); 2. Ethionine, a methionine antagonist, is a hepatocarcinogen in rats (Farber, 1963); 3. The chronic administration of the hepatocarcinogen diethylnitrosamine to rats leads to a methyl insufficiency in vivo (Poirier and Whitehead, 1973); 4. The activities of several hepatocarcinogens in rats are markedly enhanced by the concurrent feeding of lipotope-deficient (Rogers and Newberne, 1980) or choline-devoid (Lombardi and Shinozuka, 1979) diets; 5. Following initiation with liver carcinogens,