Cytochrome P-450 induction in human lung tumor-derived cell lines. Characterisation and effects of inflammatory mediators

Eur J Biochem. 1992 Sep 1;208(2):521-9. doi: 10.1111/j.1432-1033.1992.tb17216.x.


Cytochrome P-450 species (P-450) comprise a polymorphic multigene family of heme-containing enzymes which are essential to the phase-I metabolism of xenobiotics. Induction of P-450 species by drugs and carcinogens has been extensively studied; endogenous regulation of P-450 also occurs during normal development and disease. The aim of this project was to study the in-vitro induction of P-450 and its modulation by inflammatory mediators in the human lung tumor-derived cell lines NCI H322 and NCI H358. The cell lines expressed detectable levels of 7-ethoxyresorufin O-deethylase which could be induced by benzanthracene. After benzanthracene treatment, a protein tentatively identified as isozyme CYP1A1 was detected by Western-blot analysis and a concommitant increase in CYP1A mRNA expression was observed. Optimal induction was observed at a benzanthracene concentration of 5 micrograms/ml with cells grown in RPMI medium containing 10% fetal calf serum. The effects of endotoxin, dexamethasone and five recombinant DNA-derived cytokines, interleukin-1 beta, tumor necrosis factor, and interferons alpha, beta and gamma, on constitutive and benzanthracene-induced ethoxyresorufin O-deethylase activity were examined in NCI H322 cells. Of all the lymphokines studied, only interferon gamma had any marked effect. Administration of this lymphokine strongly suppressed ethoxyresorufin O-deethylase activity in both control and benzanthracene-treated cells.

MeSH terms

  • Benz(a)Anthracenes / pharmacology
  • Blotting, Western
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Cytochrome P-450 Enzyme System / genetics
  • Dexamethasone / pharmacology
  • Enzyme Induction / drug effects
  • Humans
  • Inflammation
  • Interferon-gamma / pharmacology
  • Isoenzymes / biosynthesis
  • Lung Neoplasms / enzymology*
  • Oxidoreductases / biosynthesis
  • RNA, Messenger / metabolism
  • Recombinant Proteins
  • Tumor Cells, Cultured


  • Benz(a)Anthracenes
  • Isoenzymes
  • RNA, Messenger
  • Recombinant Proteins
  • Dexamethasone
  • Interferon-gamma
  • Cytochrome P-450 Enzyme System
  • benz(a)anthracene
  • Oxidoreductases
  • Cytochrome P-450 CYP1A1