thiobenzamide and Precancerous-Conditions

S-Adenosyl-L-methionine (SAM) is a strong chemopreventive agent of rat liver carcinogenesis. Examination was made to determine whether inhibition by SAM of the development of preneoplastic liver lesions persists to SAM withdrawal in diethylnitrosamine-initiated F344 rats promoted with thiobenzamide (TB). The rats were subjected, 2 weeks after initiation, to 5 weeks feeding with a 0.1% TB diet followed by a TB-free diet for 6 weeks and then a second TB treatment for 3 weeks. SAM (384 micromol/kg/day) was injected i.m. during the first TB cycle (treatment A) or for 6 weeks after the first TB cycle (treatment B). Many gamma-glutamyltranspeptidase (GGT)-positive lesions developed in initiated rats after the first TB cycle. They decreased in number after TB withdrawal, while partial recovery of lesion number and a great increase in volume occurred after the second TB cycle. Liver ornithine decarboxylase (ODC) activity and c-myc and c-Ha-ras mRNAs increased during the TB cycles and returned to normal liver values after TB withdrawal. Number and size of GGT-positive lesions, DNA synthesis of GGT-positive cells, liver ODC activity and c-myc and c-Ha-ras mRNA levels decreased as a consequence of SAM treatment A. The recovery of these parameters, induced by a second TB cycle in rats not treated with SAM, was prevented by SAM treatment B. These results suggest that SAM causes a persistent decrease in growth capacity of preneoplastic liver lesions in rats subjected to a diethylnitrosamine/TB protocol.

Topics: Animals; Anticarcinogenic Agents; Carcinogens; Diethylnitrosamine; DNA; gamma-Glutamyltransferase; Gene Expression; Genes, myc; Genes, ras; Liver; Liver Neoplasms; Male; Ornithine Decarboxylase; Precancerous Conditions; Rats; Rats, Inbred F344; RNA, Messenger; S-Adenosylmethionine; Thioamides; Time Factors

Thiobenzamide (TB) administration to rats (1 g/Kg of diet for 4 weeks) 10 days after a single i.p. injection of dimethylnitrosamine promotes the growth of preneoplastic liver lesions as evidenced by the sharp increase in number and area of gamma-glutamyltranspeptidase-positive hepatocellular foci. At the same time the number of the plaque forming cells isolated from the spleen of rats challenged with sheep red blood cell after the completion of a TB cycle is significantly lower than in the controls 5 as well 13 days after immunization. Accordingly, TB could act as immunodepressant in the rat; this should be taken into account as far as the promoting ability of such xenobiotic is concerned.

Topics: Amides; Animals; Carcinogens; Cocarcinogenesis; Diethylnitrosamine; Female; Hemolytic Plaque Technique; Immunosuppressive Agents; Liver Neoplasms, Experimental; Precancerous Conditions; Rats; Rats, Inbred Strains; Thioamides