Persistent chemopreventive effect of S-adenosyl-L-methionine on the development of liver puptative preneoplastic lesions induced by thiobenzamide in diethylnitrosamine-initiated rats

S-Adenosyl-L-methionine (SAM) is a strong chemo-preventive agentof rat liver carcinogenesis. Examination was made to determinewhether inhibition by SAM of the development of preneoplasticliver lesions persists to SAM withdrawal in diethylnitrosamine-initiatedF344 rats promoted with thiobenzamide (TB). The rats were subjected,2 weeks after initiation, to 5 weeks feeding with a 0.1% TBdiet followed by a TB-free diet for 6 weeks and then by a secondTB treatment for 3 weeks. SAM (384 µmol/kg/day) was injectedi.m. during the first TB cycle (treatment A) or for 6 weeksafter the first TB cycle (treatment B). Many -glutamyltranspeptidase(GGT)-positive lesions developed in initiated rats after thefirst TB cycle. They decreased in number after TB withdrawal,while partial recovery of lesion number and a great increasein volume occurred after the second TB cycle. Liver ornithinedecarboxylase (ODC) activity and c-myc and c-Ha-ras mRNAs increasedduring the TB cycle. Liver ornithine decarboxylase (ODC) activityand c-myc and c-Ha-ras mRNAs increased during the TB cyclesand returned to normal liver values after TB withdrawal. Numberand size of GGT-positive lesions, DNA synthesis of GGT-positivecells, liver ODC activity and c-myc and c-Ha-ras mRNA levelsdecreased as a consequence of SAM treatment A. The recoveryof these parameters, induced by a second TB cycle in rats nottreated with SAM, was prevented by SAM treatment B. These resultssuggest that SAM causes a persistent decrease in growth capacityof preneoplastic liver lesions in rats subjected to a diethylnitrosamine/TBprotocol.