A high-level expression of CYP2A in the lung of the suncus (Suncus murinus) and its role in the activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone

Taisei Mushiroda, Noritaka Ariyoshi, Kanzo Kimura, Eiji Takahara, Osamu Nagata, Hideo Kato, Tetsuya Kamataki

Research output: Contribution to journalArticle

Abstract

Northern blot analysis of mRNA prepared from the lung of Suncus murinus (suncus), which was classified as an ancestor of primates, revealed that the expression level of cytochrome P450 2A (CYP2A) mRNA was about 100-fold higher than in the lung from rats and mice. To confirm that the pulmonary CYP2A of the suncus had a catalytic activity, the metabolism of a specific substrate for CYP2A6, (+)-cis-3,5-dimethyl-2-(3-pyridyl) thiazolidin-4-one hydrochloride (SM-12502), was determined. The intrinsic clearance for SM-12502 S-oxidation by the suncus lung microsomes was calculated to be 99-fold higher than that by rat liver microsomes. The mutagen-producing activity of a 9000 g supernatant fraction prepared from suncus lung was examined using 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) as a promutagen. The results showed that the suncus lung possessed 82-fold higher mutagen-producing activity than the rat lung, indicating that NNK was efficiently activated by the CYP2A isoform expressed in the suncus lung and that the suncus was a sensitive animal species to the genotoxicity of NNK contained in tobacco smoke. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)393-396
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume269
Issue number2
DOIs
Publication statusPublished - Mar 16 2000
Externally publishedYes

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3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one
Rats
Chemical activation
Mutagens
Lung
Messenger RNA
Tobacco
Metabolism
Smoke
Liver
Catalyst activity
Protein Isoforms
Animals
Oxidation
Substrates
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
steroid hormone 7-alpha-hydroxylase
Liver Microsomes
Microsomes
Northern Blotting

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

A high-level expression of CYP2A in the lung of the suncus (Suncus murinus) and its role in the activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. / Mushiroda, Taisei; Ariyoshi, Noritaka; Kimura, Kanzo; Takahara, Eiji; Nagata, Osamu; Kato, Hideo; Kamataki, Tetsuya.

In: Biochemical and Biophysical Research Communications, Vol. 269, No. 2, 16.03.2000, p. 393-396.

Research output: Contribution to journalArticle

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