The inhibitory effect of vitamin E on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in mice based on the regulation of polyamine metabolism.
The present study was carried out in order to estimate a usefulness of vitamin E against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in mice. Feeding high doses of vitamin E suppressed the NNK-induced elevation of the activity of ornithine decarboxylase, a key enzyme of polyamine biosynthesis, in the lungs of mice at 4 weeks after injection. In contrast, the vitamin elevated the NNK-induced decrease of the activity of spermidine/spermine N1-acetyltransferase, a key enzyme of polyamine biodegradation. In conjugation with these events, the NNK-increased level of proliferating nuclear cell antigen as a marker of cell proliferation was suppressed by vitamin E treatment. Also, the supply of high doses of vitamin E suppressed NNK-induced lung tumorigenesis in mice. These results suggest that vitamin E inhibits the development of lung tumors in mice treated with NNK, partly due to the regulation of polyamine metabolism.
Kishimoto
M
M
School of Life Environmental Science, Mukogawa Women's University, Nishinomiya, Hyogo, Japan.
Yano
Y
Y
Yajima
S
S
Otani
S
S
Ichikawa
T
T
Yano
T
T
D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000187:drug effects / Q000378:metabolism; D002273:Carcinogens; D004789:Enzyme Activation; D005260:Female; D008175:Lung Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008805:Mice, Inbred A; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism; D009602:Nitrosamines; D009955:Ornithine Decarboxylase / Q000187:drug effects / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects* / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
D002273:Carcinogens; D009363:Neoplasm Proteins; D009602:Nitrosamines; D011073:Polyamines; D018809:Proliferating Cell Nuclear Antigen; D014810:Vitamin E; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D001191:Arylamine N-Acetyltransferase; D009955:Ornithine Decarboxylase