 |
| Research article summary (published 30 Mar 2009): |
|
Free Full Text! See links below |
Enhancement of lung carcinogenesis initiated with 4-(N-hydroxymethylnitrosamino)-1-(3-pyridyl)-1-butanone by Ogg1 gene deficiency in female, but not male, mice.
Full Abstract
The present study was conducted to assess involvement of oxidative stress in lung adeno-carcinogenesis, using mice deficient in the 8-hydroxyguanine DNA glycosylase 1 (Ogg1) gene encoding an enzyme that repairs an oxidative DNA injury 8-oxoguanine (8-oxoG). Furthermore, for comparison with the human case, mutations of mouse epidermal growth factor receptor (Egfr) and K-ras genes were examined. The homo- and heterozygously Ogg1 gene-deficient and wild-type mice (C57BL6/J origin), 6 weeks old, were administered 4-(N-hydroxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by continuous subcutaneous infusion using an osmotic pump at a total dose of 6 mg/mouse for 1 week, then treated with one of 4 antioxidants (phenyl N-tert-butyl nitrone 0.13% in drinking water, resveratrol 20 ppm in diet, lactoferrin 2% in diet and bilberry powder 2% in diet) or no supplement for 33 weeks. Development of lung adenomas and preneoplastic atypical hypreplasias was significantly enhanced by the homo- and heterozygous Ogg1 gene deficiency only in female mice with intralesion accumulation of 8-oxoG. All antioxidants tended to inhibit enhanced adeno-carcinogenesis. The Egfr and K-ras gene mutations were detected at sites also found in human lung cancers with low incidences, while the Egfr gene mutation was detected for the first time in chemical lung carcinogenesis of animals. It is indicated that the Ogg1 gene deficiency enhances lung adeno-carcinogenesis in mice by virtue of accelerated oxidative stress. The presently utilized Ogg1 gene-deficient mice model may be useful to draw mechanism-based strategies to control human lung adenocarcinomas, especially in women.
Author information
Author/s: Igarashi, Maki (M); Watanabe, Manabu (M); Yoshida, Midori (M); Sugaya, Kouichi (K); Endo, Yoshifumi (Y); Miyajima, Nozomi (N); Abe, Masayoshi (M); Sugano, Sumio (S); Nakae, Dai (D);
Affiliation: Laboratory of Protection of Body Function, Department of Food and Nutritional Science, Graduate School of Agriculture, Tokyo University of Agriculture.
Journal and publication information
Publication Type: Journal Article; Research Support, Non-U.S. Gov't
Journal: The Journal of toxicological sciences (J Toxicol Sci), published in Japan. (Language: eng)
Reference: 2009-Apr; vol 34 (issue 2) : pp 163-74
Dates: Created 2009/04/01; Completed 2009/06/23;
PMID: 19336973, status: MEDLINE (last retrieval date: 6/23/2009, IMS Date: )
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
External Links for this article
(including full text providers, if available):
Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.
This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.
MeSH headings (categories)
This article was linked to the MESH Headings shown below.
Related articles
This article has not been indexed for related articles as yet, however you can still use the live related article search links below.
See a large map of 100+ related articles.