BIS(2-CHLOROETHYL)SULFIDE (BCES) DISTURBS THE PROGRESSION OF RAT KERATINOCYTES THROUGH THE CELL-CYCLE

Epidermal basal keratinocytes are the primary target in BCES-induced c utaneous injury. DNA synthesis is inhibited by exposure to BCES which could relate to the mustard's cytotoxic effect. The effects of BCES on the cell cycle in keratinocytes synchronized by aphidicolin were inve stigated. Primary keratinocytes synchronized at the G1/S boundary ente red the S, G2, M, and G1 phases at successive times after release from the block. When cells were exposed to 1, 10, or 50 mu M BCES in diffe rent phases of the cell cycle, cells in the S phase were more sensitiv e to BCES than cells in the other phases. Keratinocytes exposed to 1 m u M BCES at the G1/S boundary exhibited a prolongation of the S phase and a block in the G2 phase. When these cells were exposed to 10 or 50 mu M BCES, they did not enter the S phase for up to 12 h and the inco rporation of thymidine into DNA was inhibited. These results suggest t hat the blocks in the G2 and G1 phases relate to the cytotoxic effect of BCES on the germinative population of epidermal keratinocytes.