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 r ats were investigated by polymerase chain reaction (PCR), single stran d conformation polymorphism (SSCP) analysis followed by direct sequenc ing. Male Fischer 344 rats, 6 weeks old, were continuously given a CDA A diet for 70 weeks and then sacrificed. Macroscopically detectable no dules which were histologically confirmed to be well-differentiated HC Cs were dissected free from the surrounding tissue and subjected to ge ne mutation analysis along with samples of non-tumor areas. Conformati onal change in the Ki-ras gene was detected in 1 out of 7 HCCs, involv ing a GGC to GTC transversion at codon 13. No p53 mutations were detec ted 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 ex pose to a CDAA diet in rats.