Age dependent expression of cytochrome P-450b and metabolism of the potent carcinogen 2-nirofluorene in the rat lung

Sam Törnquist, Maria Sundin, Lennart Möller, Jan Åke Gustafsson, Rune Toftgard

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Northern and Western blot analyses, and analyses of microsomal metabolism of the carcinogen 2-nitrofluorene (NF) were conducted with the aim of studying age dependent cytochrome P-450(b) levels in the rat lung. The level of P-450(b) homologous mRNA and corresponding protein is very low in lungs from fetal and newborn rats. The levels then increase between 3 and 4 weeks of age, and reach adult levels at 6-8 weeks. No sex differences were detected with regard to lung P-450(b) mRNA levels or catalytical activities. Lung microsomal metabolism of NF increased in parallel with the accumulation of P-450(b) homologous mRNA and microsomal cytochrome P-450(b) protein concentration. Formation of the major metabolite, and potent mutagen, 9-hydroxy-2-nitrofluorene (9-OHNF) was significantly inhibited by addition of polyclonal anti-P-450(b)-IgG, and by addition of the inhibitor proadifen to incubations with lung microsomal protein. It is postulated that the observed, profound age-related differences in level and activity of lung cytochrome P-450(b) are likely to affect both availability and the ratio of metabolic detoxification and activation of chemical carcinogens deposited in the lung.

Original languageEnglish (US)
Pages (from-to)2209-2214
Number of pages6
JournalCarcinogenesis
Volume9
Issue number12
DOIs
StatePublished - Dec 1988

ASJC Scopus subject areas

  • Cancer Research

Fingerprint Dive into the research topics of 'Age dependent expression of cytochrome P-450<sub>b</sub> and metabolism of the potent carcinogen 2-nirofluorene in the rat lung'. Together they form a unique fingerprint.

Cite this