Lin P P, Bernstein I A, Vaughan F L
Toxicology Program, Department of Environmental and Industrial Health, University of Michigan, Ann Arbor, 48109-2029, USA.
Toxicol Lett. 1996 Jan;84(1):23-32. doi: 10.1016/0378-4274(95)03453-6.
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.
表皮基底角质形成细胞是BCES诱导的皮肤损伤的主要靶点。接触BCES会抑制DNA合成，这可能与芥子气的细胞毒性作用有关。研究了BCES对经阿非科林同步化的角质形成细胞细胞周期的影响。在G1/S边界同步化的原代角质形成细胞在解除阻滞释放后依次进入S期、G2期、M期和G1期。当细胞在细胞周期的不同阶段暴露于1、10或50微摩尔BCES时，S期的细胞比其他阶段的细胞对BCES更敏感。在G1/S边界暴露于1微摩尔BCES的角质形成细胞表现出S期延长和G2期阻滞。当这些细胞暴露于10或50微摩尔BCES时，它们长达12小时未进入S期，且胸苷掺入DNA受到抑制。这些结果表明，G2期和G1期的阻滞与BCES对表皮角质形成细胞生发群体的细胞毒性作用有关。
