Persistent chemopreventive effect of S-adenosyl-L-methionine on the development of liver putative preneoplastic lesions induced by thiobenzamide in diethylnitrosamine-initiated rats.
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.
Simile
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MM
Istituto di Patologia Generale e Centro di Ricerche Oncologiche, Università di Sassari, Italy.
Saviozzi
M
M
De Miglio
M R
MR
Muroni
M R
MR
Nufris
A
A
Pascale
R M
RM
Malvaldi
G
G
Feo
F
F
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002273:Carcinogens; D004247:DNA / Q000096:biosynthesis; D004052:Diethylnitrosamine; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc; D011905:Genes, ras; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D013854:Thioamides; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D012333:RNA, Messenger; D013854:Thioamides; D004052:Diethylnitrosamine; D012436:S-Adenosylmethionine; C015539:thiobenzamide; D004247:DNA; D005723:gamma-Glutamyltransferase; D009955:Ornithine Decarboxylase