Cytochrome P-450 induction in human lung tumor-derived cell lines. Characterisation and effects of inflammatory mediators.
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.
Stanley
L A
LA
Imperial Cancer Research Fund, Molecular Pharmacology Group, Edinburgh, Scotland.
Carmichael
J
J
Wolf
C R
CR
D001551:Benz(a)Anthracenes / Q000494:pharmacology; D015153:Blotting, Western; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000201:enzymology*; D010088:Oxidoreductases / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D001551:Benz(a)Anthracenes; D007527:Isoenzymes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D003907:Dexamethasone; D007371:Interferon-gamma; D003577:Cytochrome P-450 Enzyme System; C030935:benz(a)anthracene; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1