Induction of microsomal enzyme synthesis by polycyclic aromatic hydrocarbons of different molecular sizes.

The administration of various polycyclic aromatic hydrocarbons to rats markedly increases the activity of several liver enzyme systems that metabolize certain drugs and other foreign compounds (14). The enzymes which respond to hydrocarbon administration belong to a group of microsomal enzymes that require reduced triphosphopyridine nucleotide for activity. Preliminary observations have suggested the possibility that hydrocarbons may have an optimal molecular size for activity as enzyme inducers (5). In the present investigation 57 hydrocarbons differing widely in molecular size and geometry have been compared for ability to induce increases in the activity of the enzyme system in liver microsomes that N-demethylates 3methyl-4-monomethylaminoazobenzene.’ Representative hydrocarbons were also tested for (a) ability to increase the activity of the liver microsomal enzyme system that hydroxylates the muscle relaxant drug zoxazo1amine,2 and (b) ability to shorten the duration of action of a paralytic dose of zoxazolamine. Evidence is presented here that there is an optimal molecular size range for the polycyclic aromatic hydrocarbons to induce the synthesis of microsomal enzymes in the rat liver.