Effect of topical application of defined constituents of coal tar on skin and liver aryl hydrocarbon hydroxylase and 7-ethoxycoumarin deethylase activities

Abstract

A single topical application of coal tar solution (USP) to neonatal rats resulted in the induction of aryl hydrocarbon hydroxylase (AHH) and 7-ethoxycoumarin O-deethylase activities in skin, liver, lung, kidney, and intestine. The induction response of AHH in these tissues was in the order of skin > liver > intestine > lung > kidney. The induction response of 7-ethoxycoumarin O-deethylase was highest in the lung and followed the order of lung > kidney > skin > liver > intestine. Twenty-eight defined chemical constituents present in coal tar solution were individually analyzed for their induction effect on skin and liver AHH and 7-ethoxycoumarin O-deethylase activities. A single topical application of anthracene, 1,2-benzanthracene, 2,3-benzanthracene, benzo( a)pyrene, 2,3-benzofluorene, carbazole, chrysene, coronene, 1,2,3,4-dibenzanthracene, 1,2,5,6-dibenzanthracene, 7,12-dimethylbenzanthracene, fluorene, isoquinoline, 3-methylcholanthrene, or phenanthrene at a dose of 1 mg/10 g body weight to neonatal rats resulted in statistically significant induction of skin and liver AHH and 7-ethoxycoumarin O-deethylase activities. The induction response varied from chemical to chemical. Acridine was found to be an inducer of the skin enzymes only. Topical application of triphenylene, benzo(ghi)perylene, fluoranthene, 1-methylphenanthrene, and perylene caused induction of liver enzymes without producing effects on skin enzymes. These studies indicate that several hydrocarbons present in coal tar solution have induction effects on drug and carcinogen metabolism in skin and liver and that there are tissue-specific responses to some of these hydrocarbons.