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 activation of the K-ras oncogene with a 61st codon A-->T mutation at an early stage of urethane-induced lung carcinogenesis in mice. Thirty days after urethane injection, the K-ras mutation was detected in 64% of lung samples tested by mutant-allele-specific amplification. The consumption of a supplemented diet with about 20-times more vitamin E than the control diet, only during the promotion phase or during both the initiation and promotion phases of lung carcinogenesis, reduced the frequency of the mutation to 36 and 18%, respectively. Also, vitamin E suppressed the level of proliferating cell nuclear antigen as a marker of cell proliferation in the lungs of mice treated with urethane. These results support the notion that vitamin E is a useful chemopreventive agent against lung cancer.
Yano
T
T
Division of Applied Food Research, National Institute of Health and Nutrition, Tokyo, Japan. yano@nih.go.jp
Uchida
M
M
Yuasa
M
M
Murakami
A
A
Hagiwara
K
K
Ichikawa
T
T
D000818:Animals; D015139:Blotting, Southern; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D011905:Genes, ras / Q000187:drug effects* / Q000235:genetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D051379:Mice; D017354:Point Mutation / Q000187:drug effects* / Q000235:genetics; D016133:Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D014520:Urethane / Q000008:administration & dosage / Q000633:toxicity; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D014810:Vitamin E; D014520:Urethane