Similarities between mouse and rat-liver microsomal cytochromes P-450 induced by 3-methylcholanthrene. Evidence from catalytic, immunologic, and recombinant DNA studies

Anti-(P1-450) and anti-(P-448) are two antibodies developed against distinctly different forms of 3-methylcholanthrene-induced cytochrome P-450 in C57BL/6N mouse liver microsomes. The effects of these antibodies on Long-Evans and Sprague-Dawley rat liver microsomes and rat 'minimal deviation' hepatoma 7777 microsomes were studied. Rat microsomal aryl hydrocarbon hydroxylase activity, induced by polycyclic aromatic compounds, is preferentially inhibited by anti-(P1-450) more so than anti-(P-448). Polycyclic-aromatic-induced rat liver microsomal acetanilide 4-hydroxylase activity is preferentially inhibited by anti-(P-448) more so than anti-(P1-450). Anti (P1-450) precipitates a 56-kDa moiety in polycyclic-aromatic-induced rat liver microsomes. Anti-(P-448) precipitates a 55-kDa moiety in control, phenobarbital-treated, or polycyclic-aromatic-induced rat liver microsomes. A heterogeneity was found amongst individual Morris 'minimal deviation' hepatomas 7777, indicating the 3-methylcholanthrene-induced aryl hydrocarbon hydroxylase and acetanilide 4-hydroxylase activities must represent different forms of rat P-450. Clone 46 DNA, a portion of the mouse cloned P1-450 structural gene, hybridizes to one gene (or a small number of genes) in rat liver and to 3-methylcholanthrene-induced rat 23-S P1-450 mRNA. As has already been shown in the mouse rat liver P1-450 induction is under transcriptional control, and there is no evidence for gene amplification or some gross form of DNA rearrangement. These data demonstrate striking similarities between rat and mouse for the P1-450 structural gene, the P1-450 mRNA, the P1-450 protein and the P-448 protein. Polycyclic-aromatic-induced P1-450, and its association with polycyclic-aromatic-induced aryl hydrocarbon hydroxylase activity, therefore does not appear to be closely correlated with polycyclic-aromatic-induced P-448 in either rat or mouse.

Duke Scholars

Author Yuan-Tsong Chen Pediatrics, Medical Genetics