The effects of adding extra amounts of dl-methionine, choline chloride, or betaine chloride upon the occurrence of liver cancer in rats fed a 16 per cent casein diet containing 0.25 per cent ethionine was investigated. The addition of 0.6 or 0.8 per cent methionine completely prevented all the chronic morphologic changes in the liver, including liver cancer. Lower levels of methionine were partially effective. The addition of choline supplements to the ethioninecontaining diet was of limited effectiveness in reducing the incidence of liver cancer. Three levels of added choline, 0.3, 0.6, and 0.8 per cent, all exerted about an equal degree of protection. Betaine was more effective than choline and somewhat less effective than methionine in preventing liver cancer. On the basis of what is known concerning the possible importance of chronic choline deficiency in the carcinogenic action of ethionine, it is concluded that the induction of a choline deficiency is probably not an important mechanism in ethionine carcinogenesis. The preponderance of evidence favors the view that ethionine exerts its carcinogenic effect by interference with some as yet unidentified metabolic reaction of methionine.
Supported in part by grants from the American Cancer Society, the National Institute of Arthritis and Metabolic Diseases of the U. S. Public Health Service (Grant No. A-610), and the Life Insurance Medical Research Fund. A preliminary report of some of this work was presented at the 1957 annual meeting of the American Association for Cancer Research in Chicago.