Comparison of the Histological Changes in the Skin of DBA/2 and C57BL/6 Mice Following Exposure to Various Promoting Agents

The effects of multiple applications of 12-O-tetradecanoyl-phorbol-13-acetate (TPA, 6.8 nmol), teleocidin (6.8 nmol), 1,8-dihydroxy-3-methyl-9-anthrone (chrysarobin, 220 nmol), mezerein (6.8 nmol), 4-O-Methyl-TPA (4-O-Me-TPA, 150 micrograms) and benzoyl peroxide (BzP, 20 mg) on the skin of DBA/2 and C57BL/6 mice were studied histologically. After four applications of TPA given over a 2-week period, the epidermis of DBA/2 mice showed a marked epidermal hyperplasia and the presence of a much greater number of dark basal keratinocytes (DCs) 48 h after the last treatment compared with C57BL/6 mice treated with a similar dose and protocol. A marked dermal infiltration of polymorphonuclear leukocytes (PMNs) was observed in DBA/2 mice 48 h after the last application of TPA, whereas little PMN infiltration was observed in skin of C57BL/6 mice. At 96 h after the last application of TPA, DBA/2 mice still showed a much greater degree of epidermal hyperplasia than C57BL/6 mice. PMNs were virtually absent in the dermis of both DBA/2 and C57BL/6 mice by 96 h after the last TPA treatment. Interestingly, treatment of both strains of mice with multiple applications of teleocidin induced a marked epidermal hyperplasia, a high percentage of DCs and a high labeling index (LI), similar to that observed in DBA/2 mice 48 h after the last treatment. Chrysarobin (given once-weekly for 4 weeks) induced a moderate sustained hyperplasia and DC response 48 h after the last treatment in both DBA/2 and C57BL/6 mice; however, C57BL/6 mice showed a greater epidermal hyperplasia than DBA/2 mice. Chrysarobin induced a significant infiltration of PMNs into the dermis of DBA/2 mice whereas in C57BL/6 mice there was only a slight dermal infiltration of PMNs. Mezerein (given twice-weekly for 2 weeks) induced a moderate epidermal hyperplasia, DC response and LI of similar magnitude in both DBA/2 and C57BL/6 mice, but did not induce PMN infiltration in either strain. BzP and 4-O-Me-TPA (given twice-weekly for 2 weeks) induced only a weak sustained epidermal hyperplasia, DC response and LI of similar magnitude in both strains of mice, and there was little, if any, dermal infiltration of PMNs either 48 or 96 h after the last treatment. Examination of the relationship between the extent of induced hyperplasia and the DC response showed an excellent linear correlation whereas the extent of PMN infiltration into the dermis was not well correlated with either parameter.(ABSTRACT TRUNCATED AT 400 WORDS)