Infrequent Ki-ras and an absence of p53 mutations in hepatocellular carcinomas induced by a choline deficient L-amino acid defined diet in rats.
Mutations of Ki-ras and p53 genes in hepatocellular carcinomas (HCCs) induced by the choline deficient L-amino acid defined (CDAA) diet in rats were investigated by polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP) analysis followed by direct sequencing. Male Fischer 344 rats, 6 weeks old, were continuously given a CDAA diet for 70 weeks and then sacrificed. Macroscopically detectable nodules which were histologically confirmed to be well-differentiated HCCs were dissected free from the surrounding tissue and subjected to gene mutation analysis along with samples of non-tumor areas. Conformational change in the Ki-ras gene was detected in 1 out of 7 HCCs, involving a GGC to GTC transversion at codon 13. No p53 mutations were detected in 7 HCCs and also neither Ki-ras nor p53 mutations were found in non-tumor areas. The results suggest that neither Ki-ras nor p53 genes play an important role in hepatocarcinogenesis caused by long term expose to a CDAA diet in rats.
Tsujiuchi
T
T
Department of Oncological Pathology, Nara Medical University, Japan.
Kido
A
A
Nakae
D
D
Takahama
M
M
Majima
T
T
Kobitsu
K
K
Okajima
E
E
Tsutsumi
M
M
Denda
A
A
Konishi
Y
Y
D000596:Amino Acids / Q000008:administration & dosage*; D000818:Animals; D002796:Choline Deficiency / Q000150:complications*; D003062:Codon / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004032:Diet; D016158:Genes, p53; D011905:Genes, ras; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000209:etiology / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D051381:Rats
D000596:Amino Acids; D003062:Codon; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm