THE INHIBITORY EFFECT OF VITAMIN-E ON K-RAS MUTATION AT AN EARLY-STAGE OF LUNG CARCINOGENESIS IN MICE

In this study, we investigated the effect of vitamin E on the activati on of the K-ras oncogene with a 61st codon A --> T mutation at an earl y stage of urethane-induced lung carcinogenesis in mice. Thirty days a fter urethane injection, the K-ras mutation was detected in 64% of lun g samples tested by mutant-allele-specific amplification. The consumpt ion of a supplemented diet with about 20-times more vitamin E than the control diet, only during the promotion phase or during both the init iation and promotion phases of lung carcinogenesis, reduced the freque ncy of the mutation to 36 and 18%, respectively. Also, vitamin E suppr essed the level of proliferating cell nuclear antigen as a marker of c ell proliferation in the lungs of mice treated with urethane. These re sults support the notion that vitamin E is a useful chemopreventive ag ent against lung cancer. (C) 1997 Elsevier Science B.V.