The Detection Of Aflatoxin B₁-DNA Adducts And Biotransformation Enzyme CYP3A4 Levels In Primary Hepatocellular Carcinoma From Cuangxi, China

Objective: We investigate the levels of Aflatoxin B1 (AFB1) DNA adducts and its biotransformation enzyme Cytochrome P450 (CYP450) CYP3A4 in the human liver tissues from Guangxi, China, to explore the association between AFB1 exposure and its metabolism and the development of Hepatocelluar carcinoma (HCC).Methods: 151 HCC patients from Guangxi province were categorized into Southern Guangxi (SG) group (89 cases) and Northern Guangxi (NG) group (62 cases) base on their residency. 82 non-HCC patients were served as controls. Immunohistochemistry method was used to detected the levels of AFB1-DNA adducts and the expression of CYP3A4 protein in liver tissues.Results: AFB1-DNA adducts was detected in 78.8% HCC and 59.8% non-HCC liver tissues (P=0.003), but the difference between SG (78.7%) and NG (79%) group was not significant (P=1.000). AFB1-DNA adducts gray levels were (113.59±32.91) in HCC cancer tissues, (126.58±36.52) in non-HCC tissues and (139.65±29.13) in para-tumor tissues (P<0.05); and the gray levels in tumor tissues were significantly lower than its surrounding tissues in both SG group (t=-6.114,P<0.001) and NG group (t=-7.452,P <0.001). AFB1-DNA adducts gray level in cancer tissues was not significantly different between SG and NG group (F=4.280,P=0.343), but the adducts gray levels in two groups were significantly lower than that in controls (F=4.280,P<0.05). AFB1-DNA adducts gray levels in para-tumor tissues were not significantly different between SG group and NG group (F=4.828,P=0.701), but the adducts gray levels in para-tumor tissues in NG group were significantly higher than that in control group (F=4.828,P=0.010). There was close association of AFB1-DNA adducts gray levels between cancer tissues and its surrounding tissues in either SG group (r=0.436,P<0.001) or NG group (r=0.420,P=0.001). CYP3A4 gray levels were (139.15±11.82) in non-HCC tissues, (149.20±10.72) in para-tumor tissues and (166.99±19.45) in HCC cancer tissues (P<0.05); CYP3A4 gray levels in para-tumor tissues were significantly lower than its cancer tissues in either SG group (t=8.466,P<0.001) or NG group (t=5.681,P <0.001); CYP3A4 gray levels in cancer tissues were not significantly different between SG group and NG group (F=70.865,P=0.610) but the gray levels in these two groups were significantly higher than that in the non-HCC liver tissues (F=70.865,P<0.001). CYP3A4 gray levels in para-tumor tissues were not significantly different between SG group and NG group (F=21.703,P=0.677) but the gray levels in these two groups were significantly higher than that in the non-HCC liver tissues (F=21.703,P<0.001).Conclusions: we present here evidence of AFB1 exposure in liver tissues of HCC patients and non-HCC controls in Guangxi province, suggesting that universal AFB1 exposure contributes to HCC prevalence in this region. And the function and expression levels of CYP3A4 might modify the AFB1-associated hepatocarcinogenesis.