Comparative metabolism and DNA binding of 1-, 2-, and 4-nitropyrene in rats

Y. H. Chae, P. Upadhyaya, B. Y. Ji, P. P. Fu, Karam El-Bayoumy

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The metabolism and DNA binding studies of mono-NP isomers under identical conditions were conducted, as an initial investigation, in order to provide an understanding for the higher carcinogenic activity of 4-NP in the rat mammary gland. Urinary and fecal excretion patterns of 4-NP and 1-NP 24 h following administration to female CD rats tip; 24 mg/kg body weight; 1.55 mCi/rat) were similar but higher than those of 2-NP. The identified metabolites were formed via nitroreduction and ring oxidation pathways. Neither the excretion patterns nor the nature of the metabolites readily explained why the mammary tumorigenic activity of these three isomers varied. Although overall levels of mono-NP bound to liver DNA did not account for the observed differences in the biological activity, further HPLC analysis of the liver DNA hydrolysates showed that only 4-NP had yielded putative multiple DNA adducts; none were detected in the case of 1-NP and 2-NP. 1-, 2-, and 4-NP were found to bind to mammary DNA at levels of 0.6, 0.3, and 2.1 pmol/mg DNA, respectively. The structure of DNA adducts in the mammary gland and in the liver of female CD rats following the i.p. administration of 4-NP has not been identified. Collectively, the results of this preliminary study indicate that the difference in levels of DNA binding in the mammary gland in vivo may reflect why 4-NP has higher carcinogenic activity.

Original languageEnglish (US)
Pages (from-to)21-28
Number of pages8
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume376
Issue number1-2
DOIs
StatePublished - May 12 1997

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

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