INDOMETHACIN INHIBITS THE CHEMICAL CARCINOGEN BENZO(A)PYRENE BUT NOT DIMETHYLBENZ(A)ANTHRACENE FROM ALTERING LANGERHANS CELL DISTRIBUTION AND MORPHOLOGY

Treatment of murine skin with the polyaromatic hydrocarbon carcinogens benzo(a)pyrene (BP) or dimethylbenz(a)anthracene (DMBA) for 3 weeks resulted in an increase and a decrease in epidermal Langerhans cell (LC) numbers, respectively, compared with solvent-treated skin. Implantation of subcutaneous indomethacin pellets prior to carcinogen treatment prevented the changes in LC numbers and morphology in BP, but not DMBA-treated skin. Indomethacin treatment was also found to reduce elevated prostaglandin E2 (PGE)2 levels in the skin of BP-treated mice, whereas PGE2 levels were not significantly raised in DMBA-treated mice. There thus appears to be a link between altered prostaglandin levels and LC numbers in murine skin treated with BP, but not DMBA. In the latter, LC numbers were reduced by mechanisms not reversed by indomethacin. It is concluded that increased prostaglandin levels may contribute to the impairment of cutaneous immunity previously observed in BP-treated mice by altering LC density and morphology within the epidermis.