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

Autor: Michela Saviozzi, A. Nufris, Maria Rosaria De Miglio, Maria Rosaria Muroni, Maria Maddalena Simile, Gino Malvaldi, Rosa Maria Pascale, Francesco Feo
Rok vydání: 1996
Předmět:
Zdroj: Carcinogenesis. 17:1533-1537
ISSN: 1460-2180
0143-3334
DOI: 10.1093/carcin/17.7.1533
Popis: 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.
Databáze: OpenAIRE