Cytochrome P450 1A1 in rat peripheral blood lymphocytes: inducibility in vivo and bioactivation of benzo[alpha]pyrene in the Salmonella typhimurium mutagenicity assay in vitro

The presence and inducibility of CYP1A1 in freshly isolated peripheral bloo d lymphocytes was examined in untreated rats and in rats pretreated with ag ents known to induce the enzyme in other tissues, as well as dexamethasone [CAS #50-02-2], which is not commonly associated with CYP1A1 induction. CYP 1A1 but not CYP1A2 was detected by Western blot analysis of lymphocytes fro m untreated rats and was induced in lymphocytes from rats treated with the known CYP1A inducers P-naphthoflavone [CAS #6051-87-2] or 3-methylcholanthr ene [CAS #56-49-5] (7.3-fold), cigarette smoke (2.8-fold), and pyridine [CA S #108-86-1] (2.6-fold). CYP1A1 was also induced in lymphocytes from rats t reated with the nonprototypic inducer dexamethasone (17.7-fold) or bromoben zene [CAS #108-86-1] (3.9-fold). Lymphocyte homogenate from rats treated wi th the inducers also catalyzed NADPH-dependent bioactivation of benzo[a]pyr ene [CAS #50-32-8] to mutagens. The benzo(a)pyrene mutagenicity was detecte d using Salmonella typhimurium TA100 in the Ames test, and correlated posit ively 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. (C) 1999 Elsevier Scien ce B.V. All rights reserved.