STRUCTURAL GENE-PRODUCTS OF THE MURINE AH COMPLEX - DIFFERENCES IN ONTOGENESIS AND GLUCOSAMINE INCORPORATION BETWEEN LIVER MICROSOMAL CYTOCHROMES P1-450 AND P-448 INDUCED BY POLYCYCLIC AROMATIC-COMPOUNDS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 115  (3) , 585-594
Abstract
Antibodies against mouse-liver microsomal cytochromes P1-450 and P-488, 2 polycylic aromatic-inducible cytochromes, were previously developed. Liver microsomes from 3-methylcholanthrene-treated and phenobarbital-treated and control adult mice and 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated adult and fetal mice were examined. Immunoprecipitable radioactivity was measured, following labeling with pyridoxal phosphate/NaB[3H]4 or with 125I-labeled p-aminosulfobenzoic acid/NaNO2 in vitro or with [3H]leucine, [14C]glucosamine, or [32P]O4 in vivo. Induction of cytochrome P1-450 occurs developmentally earlier in gestation than induction of cytochrome P-448 when the mother is treated with polycyclic aromatic compounds. There appears to be a basal form of cytochrome P-448 but no cytochrome P1-450 in control liver microsomes; inducibility of cytochrome P-448 thus ranges between 5- and 12-fold, whereas that of P1-450 is infinite. Phenobarbital pretreatment induces no detectable P1-450 or P-448. P-448 appears to be either greater in concentration than P1-450 in the membrane or more exposed than P1-450 on the microsomal membrane surface. By the radioimmunoassay methods used, 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced P1-450 and P-448 in Ah-nonresponsive mice are indistinguishable from those in Ah-responsive mice; this is true in both the fetus and the adult. Compared with P-448 expression, the expression of P1-450 is more closely associated with 3-methylcholanthrene-induced aryl hydrocarbon hydroxylase activity, and these 2 structural gene products are apparently regulated independently. P-448 but not P1-450 appears to be a glycoprotein. These data illustrate further differences between 2 forms of polycyclic aromatic-inducible P-450 in mouse liver. Neither P1-450 nor P-448 appears to be a phosphoprotein. Neither anti-(P1-450) nor anti-(P-448) precipitates any forms of liver microsomal P-450 from .beta.-naphthoflavone-treated adult rabbits and, conversely, anti-LM4 (the antibody to rabbit liver microsomal P-450 form 4) does not precipitate any forms of liver microsomal P-450 from 3-methylcholanthrene-treated C57BL/6N mice.