Evidence that mutational activation of the ras genes may not he involved in aflatoxin B-1-induced human hepatocarcinogenesis, based on sequence analysis of the ras and p53 genes

Exposure to aflatoxin B-1 (AFB(1)) is one of the risk factors for developin g 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 o ccurs 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 transvers ion at codon 61 of the N-ras gene in a single tumor. Apparently, ras activa tion is rare in human hepatoma, and the mutation detected might not be indu ced by AFB(1). This suggests that activation of the ras gene may not be a m ajor event in AFB(1)-related human hepatocarcinogenesis. Mol. Carcinog. 26: 69-73, 1999. (C) 1999 Wiley-Liss, Inc.