Journal Article

Effects of dietary 1,4-phenylenbis(methylene)selenocyanate on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced DNA adduct formation in lung and liver of A/J mice and F344 rats

Bogdan Prokopczyk, Jonathan E. Cox, Pramod Upadhyaya, Shantu Amin, Dhimant Desai, Dietrich Hoffmann and Karam El-Bayoumy

in Carcinogenesis

Volume 17, issue 4, pages 749-753
Published in print April 1996 | ISSN: 0143-3334
Published online April 1996 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.4.749
Effects of dietary 1,4-phenylenbis(methylene)selenocyanate on
                    4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced DNA adduct formation in
                    lung and liver of A/J mice and F344 rats

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

1,4-Phenylenebis(methylene)selenocyanate (p-XSC) was tested for its ability to inhibit DNA adduct formation induced by the tobacco-specific N-nitrosamine 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in the liver and lung of A/L mice and F344 rats. Dietary p-XSC, providing a dose of 5 p.p.m. selenium, significantly inhibited the formation of 7-methylguanine (7-mGua) induced by a single i.p. injection of 10 μmol of NNK (12.8% inhibition at 4 h and 19.9% at 96 h) and O6-methylguanine (O6-mGua) (16.5% at 4 h and 34.8% at 96 h) in the liver of A/J mice. Dietary supplements of p-XSC providing 15 p.p.m. of selenium reduced the levels of 7-mGua by 17.3% (4 h) and 33.6% (96 h). The formation of O6-mGua was inhibited by 69.5% (4 h) and 73.8% (96 h). In A/J mouse lung DNA the most significant reduction was observed in levels of O6-mGua. Dietary p-XSC at 5 p.p.m. as selenium inhibited the formation of this adduct by 73.1% (4 h). Ninety-six hours after NNK injection, and at both time points with p-XSC providing 15 p.p.m. selenium,O6-mGua was not detected. Although levels of 7-mGua in mouse lung DNA were also reduced, this was significant only 4 h after carcinogen administration. In general, selenite at 5 p.p.m. as selenium had no significant effect on the levels of these lesions; however, it inhibited O6-mGua in the liver only4 h after NNK administration. These effects may explain why there is chemopreventive activity for p-XSC, but not for selenite, in NNK-induced lung carcinogenesis in A/J mice. Moreover, these findings raised our interest in determining the potential chemopreventive activity of p-XSC against NNK-induced lung adenocarcinomas in male F344 rats by first determining its effects on NNK-induced DNA methylation in the lungs of rats. Diet supplemented with 10 p.p.m. selenium as p-XSC did indeed inhibit the formation of adducts in pulmonary DNA of F344 ratstreated with four consecutive injections of 81 mg/kg of NNK. Statistically significant inhibition of O6-mGua formation was observed 4 h after carcinogen treatment in both pulmonary (49.1% inhibition) and hepatic (39.8%) DNA. Statistically significant inhibition of 7-mGua formation was also measured in lung DNA isolated 24 h after the last NNK injection (45.0%) and in liver DNA 4 h after carcinogen treatment (31.8%). Theseresults suggest that p-XSC would also inhibit induction of lung adenocarcinoma in male F344 rats by NNK.

Journal Article.  0 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.