Novel adenine adducts, N-7-guanine-AFB(1) adducts, and p53 mutations in patients with schistosomiasis and aflatoxin exposure

作者：Habib Samy L^*; Said Boctor; Awad Ahmed T; Mostafa H Mostafa; Shank Ronald C

来源：Cancer Detection and Prevention, 2006, 30(6): 491-498.

DOI：10.1016/j.cdp.2006.10.006

• novel adenine-adducts
• N-7-guanine-AFB(1)adducts
• P53 mutation
• schistosomiasis
• Synergism
• aflatoxin B-1
• S. mansoni
• S. hematobium
• cytochrome P-450
• PCR

Introduction: The most frequent mutation in human hepatocellular carcinoma (HCC) in populations exposed to a high dietary intake of aflatoxin B-1 (AFB(1)) is a mutation in codon 249 of the p53 gene. Schistosomiasis is known to cause p53 mutation. We hypothesized that the combination of schistosomiasis and aflatoxin B I increases the incidence of p53 gene mutation.
Methods: Liver tissue from 21 patients with schistosomiasis and 5 patients without schistosomiasis were analyzed for occurrence of mutations of the p53 gene and levels of N-7-guanine-AFB(1) adducts.
Results: The presence of mutations in codon 249 of p53 gene was higher in patients infected with Schistosoma haematobium (S. haematobium) than in those infected with Schistosoma mansoni (S. mansoni) or a combination of both strains (p < 0.01), compared to control subjects. No mutations were detected in p53 gene in liver DNA from schistosomiasis-free patients. Significant amounts of N-7-guanine-AFB(1) adducts and novel adenine-adducts (p < 0.01) were detected in patients with schistosomiasis, mostly in patients infected with S. haematobiton or a combination of both strains, compared to control subjects.
Conclusion: These data suggest that schistosormasis and exposure to aflatoxin B-1 act synergistically to increase the incidence of p53 gene mutation. The increase in p53 mutations may enhance progression of HCC at an early age in patients with schistosomiasis.

• 出版日期2006