The inhibitory effect of vitamin E on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced DNA injury and the fixation of the DNA injury in mouse lungs.
In order to estimate the effect of vitamin E on DNA injury and K-ras point mutation at an early stage of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK)-induced lung tumorigenesis in mice, the present study was carried out. Presupplement with vitamin E about 15 times more than control for a week significantly inhibited NNK-induced O6-methylguanine formation in the lungs of mice at 4 and 168 h after the injection. At 30 days after the NNK injection. the activation of K-ras oncogene with a 12th codon GC-->AT transition was detected in 56% of lung samples tested by mutant-allele-specific amplification. Vitamin E supplement reduced the frequency of the mutation to 30%. These results suggest that vitamin E suppresses NNK-induced DNA injury and subsequent fixation of the injury during the initiation and post-initiation phases of the lung tumorigenesis in mice.
Yano
T
T
Division of Applied Food Research, The National Institute of Health and Nutrition, Tokyo, Japan.
Yajima
S
S
Nakamura
T
T
Horikawa
S
S
Kishimoto
M
M
Ichikawa
T
T
D000818:Animals; D002273:Carcinogens / Q000009:adverse effects*; D004249:DNA Damage / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D011905:Genes, ras / Q000187:drug effects / Q000235:genetics; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control; D051379:Mice; D008815:Mice, Inbred Strains; D009602:Nitrosamines / Q000009:adverse effects*; D017354:Point Mutation / Q000187:drug effects; D016133:Polymerase Chain Reaction; D011817:Rabbits; D013047:Specific Pathogen-Free Organisms; D014810:Vitamin E / Q000494:pharmacology* / Q000627:therapeutic use
D002273:Carcinogens; D004273:DNA, Neoplasm; D009602:Nitrosamines; D014810:Vitamin E; D006147:Guanine; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C008449:O-(6)-methylguanine