REVERSAL BY 5-AZACYTIDINE OF THE S-ADENOSYL-L-METHIONINE-INDUCED INHIBITION OF THE DEVELOPMENT OF PUTATIVE PRENEOPLASTIC FOCI IN RAT-LIVER CARCINOGENESIS

被引:34
作者
PASCALE, R [1 ]
SIMILE, MM [1 ]
RUGGIU, ME [1 ]
SEDDAIU, MA [1 ]
SATTA, G [1 ]
SEQUENZA, MJ [1 ]
DAINO, L [1 ]
VANNINI, MG [1 ]
LAI, P [1 ]
FEO, F [1 ]
机构
[1] UNIV SASSARI,INST GEN PATHOL,VIA P MANZELLA 4,I-07100 SASSARI,ITALY
关键词
S-ADENOSYL-L-METHIONINE; 5-AZACYTIDINE; DNA METHYLATION; ENZYME ALTERED FOCI; RAT LIVER;
D O I
10.1016/0304-3835(91)90011-6
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The development of gamma-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-methyl-thio-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-mu-mol/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.
引用
收藏
页码:259 / 265
页数:7
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