Acnegenic activity of 3-methylcholanthrene and benzo[a]pyrene, and a comparative study with 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rabbit and hairless mouse.

The non-halogenated hydrocarbons 3-methylcholanthrene (MC) and benzo[a]pyrene (BP) were tested for acnegenic activity using the rabbit ear test. Both compounds induced characteristics follicular hyperkeratosis, although their acnegenic potency was approximately 4 orders of magnitude lower when compared to the potent acnegen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These results are discussed in view of the hypothesis that the acnegenic activity of TCDD and its congeners is mediated through stereospecific binding to a cytosolic receptor protein. In an experiment with hairless (hrhr) mice, which mutant has been described as an animal model for testing acnegenic potency, reduction in sebaceous gland tissue but no follicular hyperkeratosis was observed after application of a total dose of 0.4 microgram TCDD on the back skin. At a 10 times lower dose, no effects were seen. The hairless mouse strain used was responsive to TCDD as judged from the dose-related increase in the activity of aryl hydrocarbon hydroxylase (AHH) in liver microsomes, the increased liver weight and the histopathological changes in the liver. In comparison, a total dose of 0.12 microgram TCDD produced a strong follicular hyperkeratosis in the rabbit ear. From these results and from literature data, the adequacy of the hairless mouse for the testing of compounds for acnegenic potency is questioned.