We analyzed the adenomatous polyposis coli (APC) tumor-suppressor gene as one of the possible genes mutated in human pancreatic carcinomas. DNAs from 39 surgical specimens were subjected to single-strand conformation polymorphism analysis of polymerase chain reaction products and the mutation cluster region (MCR) of the gene was examined. We also examined the same region of DNAs from 27 surgical specimens of sporadic colon carcinomas and detected mutations in 11 carcinomas (41%). This mutation frequency in colon carcinomas was similar to those reported previously. Using this system, we detected a mutated APC gene in one of 39 pancreatic carcinomas. The results indicated that mutation of the MCR in the APC gene is involved in genesis of some of human pancreatic carcinomas, but its frequency is much lower than in colorectal carcinomas.
Summary Male F-344 rats were fed for 15 weeks a methyl-deficient L-amino acid defined diet containing 0.05% DL-ethionine. Nodules protruding from the surface of the liver were dissected free of surrounding tissue, and polyadenylated RNA isolated from the nodules was reverse transcribed. The region of the p53 gene comprising codons 120-290 was amplified by the polymerase chain reaction, and cDNAs were sequenced. Mutations were detected in nodules obtained from 7 of 12 rats. In all seven cases, the same two point mutations were present. The first was at the first base of codon 246 and consisted of a C-*T transition (C:G--T:A, Arg-*Cys), while the second was at the second base of codon 247 and consisted of a G-*T transversion (G:C->T:A, Arg->Leu). It is concluded that the hepatocarcinogen ethionine induces specific hot-spot p53 gene mutations; this is in contrast to the mutations at various sites previously observed to occur in rats fed a hepatocarcinogenic methyl-deficient diet alone. The results also provide the first evidence that ethionine is mutagenic in the rat.
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