Evidence that mutational activation of theras genes may not be involved in aflatoxin B1-induced human hepatocarcinogenesis, based on sequence analysis of theras andp53 genes

Abstract

Exposure to aflatoxin B(1) (AFB(1)) is one of the risk factors for developing hepatoma. In rats, activation of the ras gene is a prevalent event in AFB(1)-induced hepatocarcinogenesis. It is not clear whether a similar event occurs in humans. By analysis of codon 249 of the p53 gene, six of 36 human hepatoma samples were found to show a G-->T transversion, suggesting that AFB(1) may be a risk factor for hepatocarcinogenesis. However, analysis at codons 12, 13, and 61 in the ras family genes revealed a A-->T transversion at codon 61 of the N-ras gene in a single tumor. Apparently, ras activation is rare in human hepatoma, and the mutation detected might not be induced by AFB(1). This suggests that activation of the ras gene may not be a major event in AFB(1)-related human hepatocarcinogenesis.

Bibliometric analysis of the correlation between aflatoxin and hepatic carcinoma

“…[ 95 , 96 ] In rat models, sustained stimulation of the Ras oncogene is prevalent in liver malignancies initiated by AFB1 exposure. [ 97 ] It was found that mutation of the Ras oncogene induced by AFB1 led to an increase in p21 expression. In animal models, p21 positive animals showed a higher incidence of HCC than the p21 negative control group.…”

Immunohistochemical analysis of p53, cyclinD1, RB1, c-fos and N-ras gene expression in hepatocellular carcinoma in Iran

“…In our study, 83% of p53 positive samples did not show N-ras mutation. Chao et al [9] suggested that activation of the ras gene might not be a major event in aflatoxinrelated human hepatocarcinogenesis. This hypothesis is supported by another study [44] conducted in southern Africa on Blacks, where dietary exposure to aflatoxin is a risk factor.…”

Frequent k- ras -2 mutations and p16INK4Amethylation in hepatocellular carcinomas in workers exposed to vinyl chloride

“…The carcinogenic metabolite of VC, chloroethylene oxide (Przygodzki et al, 1997;Roy et al, 1998;Barbin, 1999) and a major promutagenic DNA adduct of vinyl chloride, N2,3-ethenoguanine (Dogliotti et al, 1998), produce these same mutations. Ras oncogene mutations are frequently found in chemically induced HCC in experimental animals (Chao et al, 1999;BoivinAngele et al, 2000;Xia et al, 1998), in contrast the frequency of ras mutations in human HCC is much less. To date, there are few studies on the prevalence of ras mutations in sporadic HCC of various aetiologies.…”