title: Use of cultured precision-cut rat lung slices to study the in vitro induction of pulmonary cytochrome P450 forms.
abstract: 1. The aim was to investigate the effects of some cytochrome P450 (CYP) enzyme inducers on CYP1A and CYP2B subfamily forms in cultured precision-cut rat lung slices. 2. Precision-cut lung slices were prepared from male Sprague-Dawley rats and cultured for 24 and/or 48 h in medium containing 0-20 micro g ml(-1) Aroclor 1254 (ARO), 0-50 micro M beta-naphthoflavone (BNF) and 0-50 micro M benzo(a)pyrene (BP). 3. Treatment with ARO, BNF and BP produced significant increases in lung slice whole homogenate 7-ethoxyresorufin O-deethylase activity. 4. Levels of CYP1A1 apoprotein were markedly increased in lung slice microsomes after treatment for 48 h with either 10 micro g ml(-1) ARO or 5 micro M BNF. In contrast, neither ARO nor BNF had any marked effect on levels of CYP2B1/2 apoprotein in 48-h cultured rat lung slice microsomes. 5. Real-time quantitative reverse transcription-polymerase chain reaction methodology (TaqMan) was used to quantify lung slice CYP1A1 and CYP2B1/2 mRNA levels. Rat lung slice CYP1A1 mRNA levels were increased up to 8.3-fold after treatment for 24 h with 2 and 10 micro g ml(-1) ARO, 0.5 and 5 micro M BNF, and 20 micro M BP. In contrast, treatment with 10 micro g ml(-1) ARO produced only a small 1.6-fold increase in CYP2B1/2 mRNA levels. 6. Precision-cut lung slices are a useful model in vitro system for the assessment of the effects of chemicals on pulmonary CYP forms.
authors.affiliation: BIBRA International Ltda. UK. blake@bibra.co.uk
authors.forename: B G
authors.initials: BG
authors.lastname: Lake
authors.forename: C
authors.initials: C
authors.lastname: Meredith
authors.forename: M P
authors.initials: MP
authors.lastname: Scott
authors.forename: A B
authors.initials: AB
authors.lastname: Renwick
authors.forename: R J
authors.initials: RJ
authors.lastname: Price
mesh_terms: D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000494:pharmacology; D046508:Culture Techniques / Q000295:instrumentation / Q000379:methods*; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000187:drug effects / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D051381:Rats; D016707:Tissue Fixation / Q000379:methods*; D019324:beta-Naphthoflavone / Q000494:pharmacology
chemical_list: D001140:Aroclors; D001564:Benzo(a)pyrene; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1