Simile, Maria Maddalena and Saviozzi, Michela and De Miglio, Maria Rosaria and Muroni, Maria Rosaria and Nufris, Alessandra and Pascale, Rosa Maria and Malvaldi, Gino and Feo, Francesco (1996) Persistent chemopreventive effect of S-adenosyl-L-methionine on the development of liver puptative preneoplastic lesions induced by thiobenzamide in diethylnitrosamine-initiated rats. Carcinogenesis, Vol. 17 (7), p. 1533-1537. ISSN 1460-2180. Article.
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S-Adenosyl-L-methionine (SAM) is a strong chemo-preventive 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% TBdiet followed by a TB-free diet for 6 weeks and then by a second TB treatment for 3 weeks. SAM (384 µmol/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 ϒ-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 cycle. Liver ornithine decarboxylase (ODC) activity and c-myc and c-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.
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