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 cutaneous 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 investigated. Primary keratinocytes synchronized at the G1/S boundary entered the S, G2, M, and G1 phases at successive times after release from the block. When cells were exposed to 1, 10, or 50 microM BCES in different phases of the cell cycle, cells in the S phase were more sensitive to BCES than cells in the other phases. Keratinocytes exposed to 1 microM 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 microM BCES, they did not enter the S phase for up to 12h and the incorporation of thymidine into DNA was inhibited. These results suggest that the blocks in the G2 and G1 phases relate to the cytotoxic effect of BCES on the germinative population of epidermal keratinocytes.
Lin
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PP
Toxicology Program, Department of Environmental and Industrial Health, University of Michigan, Ann Arbor, 48109-2029, USA.
Bernstein
I A
IA
Vaughan
F L
FL
D000818:Animals; D000831:Animals, Newborn; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D009151:Mustard Gas / Q000633:toxicity*; D051381:Rats; D016196:S Phase / Q000187:drug effects
D004247:DNA; D009151:Mustard Gas