Multiplicity of Cytochrome P-450 in Morris Hepatoma

Abstract

In many hepatic tumors the reduced activities of benzo[a]pyrene (BP) hydroxylase or drug-metabolizing enzymes were observed, when compared to the enzyme activities in normal adult liver, from which hepatic tumor was originated (Adamson and Fouts, 1961). Conney et al. (1957) described the remarkable and now widely recognized induction of BP hydroxylase activity in rat liver by the prior administration of BP itself, or 3-methylcholanthrene (MC), or other polycyclic hydrocarbons. An apparent induction of the drug-metabolizing enzymes by an inducer, such as MC or phenobarbital (PB), was also demonstrated in some lines of “slow-growing” Morris hepatoma (Conney and Burns, 1963; Hart et al., 1965; Watanabe et al., 1970, 1975a, 1975b), but not in Morris hepatoma 7777 (Miyake et al., 1974), Novikoff hepatoma (Hart etal., 1965), and some lines of Yoshida ascites hepatoma (Sugimura et al., 1966), all of which were considered as lines of rapidly growing tumors (Morris,1972). It was then observed that the activity and the inducibility by inducers of the drug-metabolizing enzymes were roughly correlated with the growth rate of the tumor in the host. On the other hand, very low activities of some of the drug-metabolizing enzymes were detected in the liver from newborn and fetal animals, compared with those in the liver from the corresponding adult animals (Hart et al., 1962; Watanabe et al., 1970). The inducibility of BP hydroxylation enzyme sometimes appears to be a determinant factor among those which affect the sensitivity of animals to chemical carcinogens (Watanabe et al., 1975; Nebert et al., 1978).