The frequency and mutational profile of c-H-ras gene activation were determined in sponta neous hepatocellular tumors in aged B6C3FI mice. After DNA isolation from formalin-fixed paraffin-embedded tissue sections and amplification by a polymerase chain reaction (PCR), a non-isotopic method using chemiluminescence for dot blot hybridi zation was applied to detect c-H-ras mutations. DNA sequence analysis of the c-H-ras gene from 59 hepatocellular tumors (39 carcinomas and 20 adenomas) revealed

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... t 49 (83%) contained a point mutation at codon 61. Of 34 hepatocellular carcinomas with mutations, 15 tumors (44%) had a CAA to AAA transversion at the first base of the codon, and 11 (32%) and 8 (24%) had a CAA to CTA transversion and CAA to CGA transition, respectively, at the second base. Of 15 hepatocellular adenomas with mutations, 5 (33%) had CAA to AAA, 6 (40%) CAA to CTA, and 4 (27%) CAA to CGA mutations. There was no association between the morphological features of the spontaneous mouse liver tumors and the presence or pattern of codon 61 mutations.