Differential effects of benzo[a]pyrene and dimethylbenz[a]-anthracene on Langerhans cell distribution and contact sensitization in murine epidermis

Abstract

The exposure of murine skin to potent chemical carcinogens induced distinctive effects on the distribution of epidermal Langerhans cells (LC). Our previous finding that weekly applications of 7,12-dimethylbenz[a]anthracene deplete the numbers of adenosine triphosphatase (ATPase)-positive LC was extended to show that LC are also depleted on Ia and beta-glucuronidase staining. In contrast, application of the tobacco-derived carcinogen, benzo[a]pyrene (BP), caused a significant increase in Ia-positive LC density within 2 weeks and elevated levels were maintained for up to 6 months with continuous treatment. The tobacco-derived cocarcinogenic agent, catechol, also enhanced the numbers of epidermal LC. The LC in carcinogen treated epidermis were morphologically abnormal; after BP and catechol treatment LC appeared smaller with shorter dendrites, whereas in DMBA treated epidermis LC were enlarged with elongated dendrites. Application of the contact sensitizing agent, dinitrofluorobenzene, to skin treated with BP induced hyporesponsiveness rather than contact sensitivity upon subsequent antigen challenge. Hence, the function of the large number of morphologically altered LC in BP treated skin was impaired. We conclude that carcinogen-induced alterations of LC are associated with impaired immunocompetence, although different carcinogens probably operate via different mechanisms to induce such phenomena.