Characterization of cytochromes P-450 purified from untreated and 14C-2,3,7,8-tetrachlorodibenzo-p-dioxin - treated marmoset monkeys: Identification of the major form as a possible orthologue of P-450 1A2

Abstract Three purified cytochrome P -450 ( P -450) forms obtained from liver microsomes of marmoset monkes induced with 14 C-2,3,7,8-tetrachlorodibenzo- p -dioxin ( 14 C-TCDD) were characterized. Comparison of electrophoretic and spectral properties and reconstituted methoxy-and ethoxyresorufni O -dealkylase (MROD adn EROD) activities with those of forms isolated from untreated marmosets indicated that one of these (form F) is likely constitutive. another form (D) had MROD and EROD activities which were 100 and 15 times those obserbed for form F. A form having biophysical properties similar to those of form D was also found in untreated animals. A third form (C) had an appreciable capacity to bind its inducing agent and showed a TCDD-to- P -450 molar ratio for detergent-free solutions of 0.66 ± 0.13 to 1. In immunoblot analyses of these forms with antibodies raised against specific peptide sequences derived from rat P -450 1A1 and 1A2, the only ositive reactions seen were those for untreated and inducible forms D with anti-rat 1A2. This provides evidence that the main or sole P -450 1A form in marmoset liver microsomes is 1A2, as in humans, and that this is inducible by TCDD.