Cytochrome P450 1A1 in rat peripheral blood lymphocytes: inducibility in vivo and bioactivation of benzo[a]pyrene in the Salmonella typhimurium mutagenicity assay in vitro.
The presence and inducibility of CYP1A1 in freshly isolated peripheral blood lymphocytes was examined in untreated rats and in rats pretreated with agents known to induce the enzyme in other tissues, as well as dexamethasone [CAS #50-02-2], which is not commonly associated with CYP1A1 induction. CYP1A1 but not CYP1A2 was detected by Western blot analysis of lymphocytes from untreated rats and was induced in lymphocytes from rats treated with the known CYP1A inducers beta-naphthoflavone [CAS #6051-87-2] or 3-methylcholanthrene [CAS #56-49-5] (7.3-fold), cigarette smoke (2. 8-fold), and pyridine [CAS #108-86-1] (2.6-fold). CYP1A1 was also induced in lymphocytes from rats treated with the nonprototypic inducer dexamethasone (17.7-fold) or bromobenzene [CAS #108-86-1] (3. 9-fold). Lymphocyte homogenate from rats treated with the inducers also catalyzed NADPH-dependent bioactivation of benzo[a]pyrene [CAS #50-32-8] to mutagens. The benzo(a)pyrene mutagenicity was detected using Salmonella typhimurium TA100 in the Ames test, and correlated positively with lymphocyte CYP1A1 content. The data show that CYP1A1 is present in rat peripheral blood lymphocytes in vivo, and is inducible by prototypic, as well as nonprototypic, inducers of the enzyme.
Fung
J
J
Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ 08855, USA.
Thomas
P E
PE
Iba
M M
MM
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D015153:Blotting, Western; D001969:Bromobenzenes / Q000633:toxicity; D019363:Cytochrome P-450 CYP1A1 / Q000097:blood*; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D008214:Lymphocytes / Q000201:enzymology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects; D019324:beta-Naphthoflavone / Q000494:pharmacology
D001969:Bromobenzenes; D009153:Mutagens; D011725:Pyridines; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; D019324:beta-Naphthoflavone; D003907:Dexamethasone; C032036:bromobenzene; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; C023666:pyridine