Induction of dimethylnitrosamine demethylase activity in mouse liver by polychlorinated biphenyls and 3-methylcholanthrene

Abstract

Hepatic dimethylnitrosamine (DMN) demethylase activity in male C57BL/6 mice, assayed with 1 or 5 mM DMN and expressed per g liver, increased after i.p. treatment with Aroclor 1254 [polychlorinated biphenyls (PCBS), 500 mg/kg, 96 hr before assay], compared with parallel oil-injected controls. This increase was of statistical significance when either the postmitochondrial supernatant fraction (sup) or isolated microsomes were assayed. The induction appeared larger with 5 mM DMN as substrate (about 180 per cent) than with 1 mM DMN (about 65 per cent). PCBs also induced sup DMN (5 mM) demethylase activity in (C57BL/6 × BALB/c)F 1 and Swiss-Webster mice. 3-Methyl-cholanthrene exposure (80 mg/kg, 48 hr) resulted in a small but significant increase in sup hepatic DMN (5 mM) demethylase activity in C57BL/6 and F 1 mice. Isolated microsomes from C57BL/6 livers exhibited only 40–60 per cent of the DMN (1 or 5 mM) demethylase activity present in the corresponding sup; such preparations may not give an accurate indication of in vivo activity. Inclusion of the lipid layer with the sup resulted in a significant increase in DMN (5 mM) demethylase activity in Aroclor-induced, but not in control, C57BL/6 mouse livers. The number of cells per unit area of liver, determined microscopically after treatment of C57BL/6 mice with PCBs, decreased slightly (15 per cent) but significantly compared with controls. Thus, enzyme activity per g liver represents a conservative approximation of activity per cell, which is the parameter that should be measured for demonstration of induction or repression and for evaluation of potential toxic or carcinogenic effects.