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

Carcinogenesis. 1988 Dec;9(12):2209-14. doi: 10.1093/carcin/9.12.2209.

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-450b levels in the rat lung. The level of P-450b 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-450b mRNA levels or catalytical activities. Lung microsomal metabolism of NF increased in parallel with the accumulation of P-450b homologous mRNA and microsomal cytochrome P-450b 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-450b-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-450b are likely to affect both availability and the ratio of metabolic detoxification and activation of chemical carcinogens deposited in the lung.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Acetylaminofluorene / metabolism
  • Aging / metabolism*
  • Animals
  • Carcinogens / metabolism*
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Cytochrome P-450 Enzyme System / genetics
  • Female
  • Fluorenes / metabolism*
  • Hydroxylation
  • Immunoblotting
  • In Vitro Techniques
  • Isoenzymes / biosynthesis
  • Lung / metabolism*
  • Male
  • Microsomes / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred Strains

Substances

  • Carcinogens
  • Fluorenes
  • Isoenzymes
  • RNA, Messenger
  • 2-nitrofluorene
  • Cytochrome P-450 Enzyme System
  • 2-Acetylaminofluorene