Reversal by 5-azacytidine of the S-adenosyl-L-methionine-induced inhibition of the development of putative preneoplastic foci in rat liver carcinogenesis
R Pascale, MM Simile, ME Ruggiu, MA Seddaiu… - Cancer letters, 1991 - Elsevier
R Pascale, MM Simile, ME Ruggiu, MA Seddaiu, G Satta, MJ Sequenza, L Daino…
Cancer letters, 1991•ElsevierThe development of γ-glutamyltranspeptidase (GGT)-positive foci, in Wistar rats, initiated
with diethylnitrosamine and subjected to selection according to 'resistant
hepatocyte'protocol, was coupled, 7 weeks after initiation, with liver DNA hypomethylation
and with a fall in S-adenosylmethionine/S-adenosylhomocysteine (SAM SAH) ratio, and in 5-
methylthio-adenosine (MTA) content. A 15-day treatment with SAM, started 1 week after
selection, caused a dose-dependent decrease in the development of GGT-positive foci …
with diethylnitrosamine and subjected to selection according to 'resistant
hepatocyte'protocol, was coupled, 7 weeks after initiation, with liver DNA hypomethylation
and with a fall in S-adenosylmethionine/S-adenosylhomocysteine (SAM SAH) ratio, and in 5-
methylthio-adenosine (MTA) content. A 15-day treatment with SAM, started 1 week after
selection, caused a dose-dependent decrease in the development of GGT-positive foci …
The development of γ-glutamyltranspeptidase (GGT)-positive foci, in Wistar rats, initiated with diethylnitrosamine and subjected to selection according to ‘resistant hepatocyte’protocol, was coupled, 7 weeks after initiation, with liver DNA hypomethylation and with a fall in S-adenosylmethionine/S-adenosylhomocysteine (SAM SAH) ratio, and in 5-methylthio-adenosine (MTA) content. A 15-day treatment with SAM, started 1 week after selection, caused a dose-dependent decrease in the development of GGT-positive foci, recovery of liver SAM SAH ratio and MTA level, and liver DNA methylation. A 12-day treatment with 20 μmol/kg per day of 5-azacytidine (AzaC), starting 1 week after selection, enhanced growth of GGT-positive foci, caused strong DNA hypomethylation, and partially counteracted the inhibition of GGT-positive foci growth, without affecting recovery of SAM SAH ratio and MTA level, induced by SAM. These results suggest a role of DNA methylation in the antipromoting effect of SAM.
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