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.
Three purified cytochrome P-450 (P-450) forms obtained from liver microsomes of marmoset monkeys induced with 14C-2,3,7,8-tetrachlorodibenzo-p-dioxin (14C-TCDD) were characterized. Comparison of electrophoretic and spectral properties and reconstituted methoxy-and ethoxyresorufin O-dealkylase (MROD and 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 observed 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 positive 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.
Kastner
M
M
Freie Universität Berlin, Institut für Toxikologie und Embryopharmakologie, Germany.
Neubert
D
D
D000818:Animals; D002427:Cebidae; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification; D004790:Enzyme Induction / Q000187:drug effects; D007527:Isoenzymes / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*
D007527:Isoenzymes; D000072317:Polychlorinated Dibenzodioxins; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2