In vitro aflatoxin B1-induced p53 mutations.
The tumor suppressor gene p53 is commonly mutated with high frequencies at certain hot spots in human cancers. In liver cancers there is an especially high frequency of mutations at codon 249. To study the impact of carcinogen targeting and the role of cytosine methylation on the mutation spectrum, a common liver cancer carcinogen aflatoxin B1 (AFB1), was studied using the p53 cDNA template to examine mutation induction. Subsequent mutations were detected with a yeast p53 functional assay and identified by DNA sequencing. The results indicated that cytosine methylation enhances AFB1-induced guanine mutations at CpG sites. However, no mutations were detected at codon 249.
Chan
Kin-Tak
KT
Department of Biology, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong (SAR), China.
Hsieh
Dennis Paul Hsientang
DP
Lung
Maria Li
ML
D016604:Aflatoxin B1 / Q000633:toxicity*; D001483:Base Sequence; D002273:Carcinogens; D003062:Codon / Q000235:genetics; D019175:DNA Methylation; D017931:DNA Primers; D018076:DNA, Complementary; D015226:Dinucleoside Phosphates / Q000378:metabolism; D016158:Genes, p53 / Q000187:drug effects*; D009153:Mutagens; D010957:Plasmids / Q000187:drug effects / Q000235:genetics; D016133:Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics*; D013698:Templates, Genetic
D002273:Carcinogens; D003062:Codon; D017931:DNA Primers; D018076:DNA, Complementary; D015226:Dinucleoside Phosphates; D009153:Mutagens; D016604:Aflatoxin B1