INFLAMMATORY RESPONSE OF MOUSE SKIN EXPOSED TO THE VERY POTENT CARCINOGEN DIBENZO[A,L]PYRENE - A MODEL FOR TUMOR PROMOTION

The potent carcinogenicity of dibenzo[a,l]pyrene in mouse skin is asso ciated with an inflammation unique among polycyclic aromatic hydrocarb ons and expressed as erythema. The time course of erythema and the ass ociated histological events in the skin of female SENCAR mice were det ermined after a single application of 6.25-200 nmol dibenzo[a,l]pyrene or selected metabolites, Dibenzo[a,l]pyrene and dibenzo[a,l]pyrene-11 ,12-dihydrodiol, precursor to the bay-region diol epoxide, induced an erythema first present 5-6 days after treatment. Dibenzo[a,l]pyrene-8, 9-dihydrodiol and other dibenzo[a,l]pyrene metabolites, however, did n ot induce erythema. These findings suggest a central role for the bay- region diol epoxide in the induction of the observed inflammation. The intensity and duration of erythema were dose-dependent, whereas the d elayed appearance of erythema was constant and dose-independent. These results suggest induction of an immune hypersensitivity by dibenzo[a, l]pyrene and its 11,12-dihydrodiol. Histological changes in the skin w ere consistent with a contact hypersensitivity reaction and included, in association with erythema, epidermal hyperplasia and the presence o f mononuclear leukocytes in the dermis. Animals were tested for dibenz o[a,l]pyrene-induced contact hypersensitivity. Female SENCAR mice were treated with a single dermal application of dibenzo[a,l]pyrene or 7,1 2-dimethylbenz[a]anthracene. Five days later, the animals were challen ged with a single application of dibenzo[a,l]pyrene or 7,12-dimethylbe nz[a]anthracene to the ear pinna. Ear swelling exhibited features of a contact hypersensitivity reaction, including (1) delayed appearance a fter challenge, (2) noninducibility in animals not previously exposed to chemical sensitizer, and (3) chemical specificity. The results sugg est that dibenzo[a,l]pyrene induces, via its bay-region diol epoxide, a contact hypersensitivity reaction that may promote tumor development and thereby enhance carcinogenic potency. (C) 1997 Society of Toxicol ogy.