TY - JOUR
T1 - DNA methylation patterns of the rat gamma-glutamyl transpeptidase gene in embryonic, adult and neoplastic liver
AU - Baik, Ja Hyun
AU - Griffiths, Susan
AU - Giuili, Galicia
AU - Manson, Margaret
AU - Siegrist, Sylvie
AU - Guellaen, Georges
N1 - Funding Information:
The authors would like to thank Dr A.G Smith and Dr B.G.Lake for providing tissue samples from hexachlorobenzene-, diethylnitrosamine-and nafenopin-treated animals and for helpful discussions. We thank Dr Y.Laperche and Dr R.Barouki for their most helpful comments and L.Rosario and E.Grandvilliers for their skilful secretarial assistance. Susan Griffiths was funded by the Association for International Cancer Research. This work was supported by the CNAMTS.
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 1991/6
Y1 - 1991/6
N2 - The methylation status of the rat gamma-glutamyl transpeptidase (GGT) gene was investigated during liver development and hepatocarcinogenesis. The analysis with the restriction enzymes MspI/HpaII revealed that, during ontogeny, there is a progressive methylation of the GGT gene that coincides with a progressive decrease in GGT activity. Thus, there is an inverse correlation between methylation and expression of the GGT gene, suggesting a role for DNA methylation in the regulation of the gene during normal differentiation. The methylation patterns of the GGT gene in liver tumours induced by aflatoxin B1 exhibit heterogeneity. Nevertheless, a band of 5.7 KB was observed in all the DNA samples from aflatoxin B1-induced tumours which was not present in control liver DNA. The specificity of the DNA methylation changes was assessed using nafenopin, which induces hepatic tumours without elevation of GGT activity. We conclude that, during hepatocarcinogenesis, there is a modification of the DNA methylation pattern of the GGT gene, but there is no simple correlation with GGT activity. In no case was the GGT gene methylation in hepatocarcinogenesis found to be equivalent to the pattern observed in fetal liver. Thus if methylation is involved in the regulation of GGT gene transcription, the mechanisms must be different in fetal liver and hepatocarcinoma.
AB - The methylation status of the rat gamma-glutamyl transpeptidase (GGT) gene was investigated during liver development and hepatocarcinogenesis. The analysis with the restriction enzymes MspI/HpaII revealed that, during ontogeny, there is a progressive methylation of the GGT gene that coincides with a progressive decrease in GGT activity. Thus, there is an inverse correlation between methylation and expression of the GGT gene, suggesting a role for DNA methylation in the regulation of the gene during normal differentiation. The methylation patterns of the GGT gene in liver tumours induced by aflatoxin B1 exhibit heterogeneity. Nevertheless, a band of 5.7 KB was observed in all the DNA samples from aflatoxin B1-induced tumours which was not present in control liver DNA. The specificity of the DNA methylation changes was assessed using nafenopin, which induces hepatic tumours without elevation of GGT activity. We conclude that, during hepatocarcinogenesis, there is a modification of the DNA methylation pattern of the GGT gene, but there is no simple correlation with GGT activity. In no case was the GGT gene methylation in hepatocarcinogenesis found to be equivalent to the pattern observed in fetal liver. Thus if methylation is involved in the regulation of GGT gene transcription, the mechanisms must be different in fetal liver and hepatocarcinoma.
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U2 - 10.1093/carcin/12.6.1035
DO - 10.1093/carcin/12.6.1035
M3 - Article
C2 - 1675160
AN - SCOPUS:0025762322
SN - 0143-3334
VL - 12
SP - 1035
EP - 1040
JO - Carcinogenesis
JF - Carcinogenesis
IS - 6
ER -
