Low frequency of p53 gene mutation in tumors induced by aflatoxin B1 in nonhuman primates.
Aflatoxin B1 has been suggested as a causative agent for a G to T mutation at codon 249 in the p53 gene in human hepatocellular carcinomas from southern Africa and Qidong in China. To test this hypothesis, nine tumors induced by aflatoxin B1 in nonhuman primates were analyzed for mutations in the p53 gene. These included four hepatocellular carcinomas, two cholangiocarcinomas, a spindle cell carcinoma of the bile duct, a hemangioendothelial sarcoma of the liver, and an osteogenic sarcoma of the tibia. None of the tumors showed changes at the third position of codon 249 by cleavage analysis of the HaeIII enzyme site at codon 249. A point mutation was identified in one hepatocellular carcinoma at the second position of codon 175 (G to T transversion) by sequencing analysis of the four conserved domains (II to V) in the p53 gene. These data suggest that mutations in the p53 gene are not necessary in aflatoxin B1 induced hepatocarcinogenesis in nonhuman primates. The occurrence of mutation in codon 249 of the p53 gene in selective samples of human hepatocellular cancers may indicate involvement of environmental carcinogens other than aflatoxin B1 or that hepatitis B virus-related hepatitis is a prerequisite for aflatoxin B1 induction of G to T transversion in codon 249.
Fujimoto
Y
Y
Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892.
Hampton
L L
LL
Luo
L D
LD
Wirth
P J
PJ
Thorgeirsson
S S
SS
D002759:Adenoma, Bile Duct / Q000139:chemically induced; D016604:Aflatoxin B1 / Q000633:toxicity*; D000818:Animals; D001483:Base Sequence; D001650:Bile Duct Neoplasms / Q000139:chemically induced; D001859:Bone Neoplasms / Q000139:chemically induced; D002277:Carcinoma / Q000139:chemically induced; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D016158:Genes, p53 / Q000187:drug effects; D006390:Hemangioendothelioma / Q000139:chemically induced; D007438:Introns; D008113:Liver Neoplasms / Q000139:chemically induced; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009374:Neoplasms, Experimental / Q000235:genetics*; D009838:Oligodeoxyribonucleotides; D012516:Osteosarcoma / Q000139:chemically induced; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm; D009838:Oligodeoxyribonucleotides; D016604:Aflatoxin B1