Induction of N-nitrosodimethylamine metabolism in liver and lung by in vivo pyridine treatments of rabbits

Date

2000-08-01

Author

Arinc, E
Adalı, Orhan
Gencler-Ozkan, AM

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N-Nitrosodimethylamine is a procarcinogen that is activated by cytochrome P450 dependent N-nitrosodimethylamine N-demethylase to labile alpha-carbon hydroxylated products further resulting in active methylating agents. In vivo intraperitoneal administration of pyridine to rabbits significantly increased N-nitrosodimethylamine N-demethylase activity by 6.9- and 5.2-fold in liver and lung microsomes, respectively. Although, p-nitrophenol hydroxylase and aniline 4-hydroxylase activities were markedly enhanced by pyridine treatment in liver about 4.4- and 5.8-fold, respectively, no change was observed in the activities of these enzymes in lung microsomes. Pyridine treatment also elevated P450 contents of liver and lung by 2.04- and 1.4-fold, respectively. SDS-PAGE of pyridine-induced liver microsomes revealed a protein band of enhanced intensity having M-r of 51,000 migrating in the region of cytochrome P4502E1. The results obtained in this study demonstrated for the first time, a significant 5.2-fold induction of NDMA N-demethylase activity in the rabbit lung over the controls. Pyridine is readily absorbed by inhalation and is a constituent of tobacco and tobacco smoke. Thus induction of NDMA N-demethylase suggests that in the lung, as in the liver, pyridine may stimulate the metabolic activation of this nitrosamine significantly.

Subject Keywords

N-Nitrosodimethylamine, Pyridine, Procarcinogen, Liver, Lung, Induction, Rabbit

URI

https://hdl.handle.net/11511/36694

Journal

ARCHIVES OF TOXICOLOGY

DOI

https://doi.org/10.1007/s002040000108

Collections

Department of Biology, Article

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Citation Formats

E. Arinc, O. Adalı, and A. Gencler-Ozkan, “Induction of N-nitrosodimethylamine metabolism in liver and lung by in vivo pyridine treatments of rabbits,” ARCHIVES OF TOXICOLOGY, pp. 329–334, 2000, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/36694.