The effect of aflatoxin B_1 and HBV X gene on expression profiles of drug-meta bolizing enzymes genes in transgenic mice with HBVx gene by cDNA microarray

Objective To investigate difference of gene expression profiles for drug-metabolizing enzymes by AFB 1 treatment and HBV X gene expression inducing hepatocarcinogenesis in transgenic mice with HBVx gen e and to explore the molecular mechanism of the synergetic hepatocarcinogenesis effect of both HBV and AFB 1 in the development of HCC.Methods Using BiostarM-40s cDNA microarray to analyze the diff erent expression of liver tissues between the blank group and the experimental g roups including HBVx group, AFB 1 group and the combine group of HBVx and AFB 1.Results Evident difference was observed in experimental groups when compared with the blank group. The number of aberrant expressions including up-regulated and down-regulated genes in HBVx group, AFB 1 group and the com bine group were 35,101 and 69,respectively. We also found 18 aberrant expression which involved in metabolizing enzymes, among 18 genes, 4 out of 18 (22%) in HB Vx group, 8 out of 18 (44%) in AFB 1 group and 13 out of 18 (72%) in the combin e group.Conclusion The gene expression levels of those genes encoding d rug-metabolizing enzymes including GST,EPHX and UDPGT are significantly lower in mice, which suffered from dual attack of HBV X gene plus AFB 1 than in those which suffered from single attack of HBV X gene or AFB 1.The mechanisms of HBV and AFB 1-induce synergetic hepatocarcinogenesis may be correlation with the expression levels down-regulated of drug-metabolizing enzymes genes.