Monoclonal antibodies to rabbit liver cytochrome P450 LM2.

The mixed-function oxidases containing cytochrome P450 are the primary systems that metabolize xenobiotics including drugs and carcinogens and endogenous substrates such as steroids [l-3]. The mixed-function oxidases may be key determinants of the rates of drug metabolism [2] and carcinogen susceptibility [3-S]. A major class of carcinogens to which humans are exposed is the polycyclic aromatic hydrocarbons. A prototype and most common hydrocarbon of this class is benzo [a] pyrene (BP) [6]. Benzo [alpyrene is oxidized by the mixed-function oxidase, aryl hydrocarbon hydroxylase (AHH) and metabolically related enzymes to >40 oxygenated metabolites which include simple epoxides, phenols, quinones, dihydrodiols, diol epoxides and water-soluble conjugates of glutathione, glucuronide and sulfate [7]. The pathway leading to the benzo [a] pyrene diol epoxides is believed to be a primary pathway of carcinogen activation [7]. Different forms of cytochrome P450 have been isolated and characterized (reviewed [8]). Cytochromes P450 LM2 and LM4 have been purified to homogeneity [9-l l] and P450 LMI, LM3 and LM7 have been partially purified [9] from rabbit liver. The highly purified LM2 and LM4 exhibit different biochemical, immunological and kinetic properties [ 121. Furthermore each isozyme of P450 exhibits stereoselectivity in substrate choice and product formation with respect to both benzo[a]pyrene metabolism and the conversion of (-)t-7,8-diol benzo[a]pyrene into the highly mutagenic benzo [a] pyrene 7,&diol9,1 Oepoxides [13,14]. Immunoglobulin genes derived from mouse-spleen cells primed with specific antigens are expressed and