Metabolism of 2,4,5,2',5'-pentachlorobiphenyl by lung and liver microsomes

Abstract

Earlier studies on distribution, excretion and metabolism of 14C-2,4,5,2',5'-pentachlorobiphenyl (PCB) in mouse and monkey have shown the presence of two mono-hydroxylated metabolites in feces, a high concentration of radioactivity in liver and an accumulation of radioactivity in the lung, especially in the bronchial epithelium. An investigation has therefore been made to study the metabolism on the microsomal fractions of lung and liver from mouse, rat, monkey and man and on the microsomal fractions of lung and liver from rats pretreated with methylcholanthrene (MC) or phenobarbital (PB). The results show great species differences - in mouse and rat, lung microsomes metabolize PCB faster than liver microsomes, giving one metabolite in lung and two in liver, while in monkey and man only liver microsomes metabolize PCB, giving one dominating metabolite. Aromatic hydrocarbons are known to be metabolized by the P-450-dependent aryl hydrocarbon hydroxylase (AHH) system. It is also known that there is both intra- and inter-differences in the AHH concentration. This fact, together with the fact that P-450 consists of several components with probably different functions in metabolism, could be the reason that there is no correlation between the two groups of species in this investigation. The investigation also shows the danger in studying the toxicity in mouse or rat, taking it for granted that the toxicity is the same for man.