| Автор | Foiles, Peter G. |
| Автор | Trushin, Neil |
| Автор | Castonguay, Andre |
| Дата выпуска | 1985 |
| dc.description | Rabbit antibodies raised against O<sup>6</sup>-methy1-2'-deoxyguanosine (O<sup>6</sup>-MedGuo) were used to develop a competitive BiotinAvidin enzyme-linked immunosorbent assay (BA-ELISA) for the quantitation of this adduct in DNA from animals exposed to tobacco-specific N-nitrosamines. The assay was able to detect as little as 30 μmol O<sup>6</sup>-MedGuo per mol deoxyguanosine. The specificity of the assay was at least 10 000-fold greater for O<sup>6</sup>-MedGuo than for unmodified nucleosides or 7-methyl-2'-deoxyguanosine. The sensitivity of the assay was increased to 1 μmol O<sup>6</sup>-MedGuo per mol deoxyguanosine by the prior separation of O<sup>6</sup>-MedGuo from unmodified nucleosides by h.p.l.c. This assay was used to study the methyiating ability of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in F344 rats. Four hours after exposure to a single i.v. dose of NNK O<sup>6</sup>-MedGuo was detected in the target tissues nasal mucosa, lung and liver (219, 13.2 and 34.5 μmol/mol deoxyguanosine) but not in the non-target tissues esophagus, spleen, heart or kidney. Chronic exposure by 14 daily i.p. injections of NNK also resulted in detectable amounts of O<sup>6</sup>-MedGuo in the lung and nasal mucosa (11.4 and 7.9 μmol/mol deoxyguanosine). These results demonstrate that NNK is capable of methylating DNA in vivo. The methodology developed in these studies will allow us to examine in detail the role of DNA methylation in NNK-mediated carcinogenesis. |
| Формат | application.pdf |
| Издатель | Oxford University Press |
| Копирайт | © 1985 IRL Press Ltd. |
| Тема | ORIGINAL ARTICLES |
| Название | Measurement of O<sup>6</sup>-methyldeoxyguanosine in DNA methylated by the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone using a biotin-avidin enzyme-linked immunosorbent assay |
| Тип | other |
| Electronic ISSN | 1460-2180 |
| Print ISSN | 0143-3334 |
| Журнал | Carcinogenesis |
| Том | 6 |
| Первая страница | 989 |
| Последняя страница | 993 |
| Аффилиация | Naylor Dana Institute for Disease Prevention, American Health FoundationValhalla, NY 10595, USA |
| Выпуск | 7 |
