Induction of CYP1A1 and CYP1A2 expressions by prototypic and atypical inducers in the human lung.
The inducibility of cytochrome P4501A1 gene (CYP1A1) expression was examined in human lung samples from 27 subjects, using an explant culture system and semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. CYP1A1 transcripts were present in all of the lung specimens and were induced by the prototypic inducers 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and benzo[a]pyrene (B[a]P), and by the atypical inducers pyridine, nicotine, and omeprazole. 2-Hydroxypyridine was a better inducer than pyridine, implicating metabolites in CYP1A1 induction by the parent compound. The prototypical inducers were the most effective inducers in many samples but were ineffective in some samples in which the atypical compounds were effective inducers. Cytochrome P4501A2 (CYP1A2) transcripts were also detected in most of the lung specimens and were inducible in some specimens. The results show the suitability of the explant culture system for examining the inducibility of human pulmonary CYP1A1 and CYP1A2, indicate the heterogeneity in individual sensitivity to the induction, and underscore the need to include atypical inducers in studies of CYP1A inducibility in humans.
Wei
Cindy
C
Department of Pharmacology and Toxicology, Rutgers University, EOHSI Building, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA.
Caccavale
Robert J
RJ
Weyand
Eric H
EH
Chen
Suzie
S
Iba
Michael M
MM
D001564:Benzo(a)pyrene / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000494:pharmacology; D004790:Enzyme Induction; D005731:Ganglionic Stimulants / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014020:Tissue Extracts
D004785:Environmental Pollutants; D005731:Ganglionic Stimulants; D000072317:Polychlorinated Dibenzodioxins; D011725:Pyridines; D012333:RNA, Messenger; D014020:Tissue Extracts; D001564:Benzo(a)pyrene; D009538:Nicotine; D004247:DNA; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; C023666:pyridine