FREQUENCY OF RAS MUTATIONS IN LIVER NEOPLASMS FROM B6C3F(1) MICE EXPOSED TO TETRAFLUOROETHYLENE FOR 2 YEARS

Tetrafluoroethylene (TFE) was evaluated for carcinogenicity in inhalat ion studies because of its high use in the production of Teflon. There was clear evidence of hepatocarcinogenic activity in B6C3F(1) mice af ter 2 yr of TFE exposure. The present study was designed to characteri ze the mutation profiles of H- and K-ras oncogenes in liver neoplasms in mice after exposure to 0, 312, 625, or 1,250 ppm TFE. ras mutations were identified by restriction fragment length polymorphism, single-s tranded conformation polymorphism analysis, and direct sequencing of p olymerase chain reaction amplified-DNA isolated from frozen or paraffi n-embedded liver neoplasms. A low frequency (15%, 9/59) of H-ras codon 61 mutations was detected in hepatocellular neoplasms when compared w ith the higher frequency (59% of this study and 56% of historical data ) in spontaneously occurring liver neoplasms. There was no difference in the mutation frequency or spectrum among exposure groups or between benign and malignant hepatocellular neoplasms. K-ras mutations at cod ons 12, 13, and 61 and H-ras mutations at codon 117 were not detected in hepatocellular neoplasms. These data suggest that TFE-induced hepat ocellular neoplasms are developed by pathways that are mostly independ ent of ras mutations. The ras mutation frequency and spectrum were sim ilar to those of the structurally related chemical tetrachloroethylene .