Effects of commonly used mitogens on the cytotoxicity of 4-tertiary butylphenol to human melanocytes.
Effects of commonly used mitogens on the cytotoxicity of 4-tertiary butylphenol to human melanocytes.
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常用促细胞分裂剂对 4-叔丁基苯酚对人黑素细胞细胞毒性的影响。
DOI：
10.1007/s11626-999-0094-5
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Boissy,RE
中科院分区：
文献类型：
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作者：
Yang,F;Abdel-Malek,Z;Boissy,RE
在寻找负责接触或职业性白癜风的环境化合物时，发现最有效的是4-叔丁基苯酚（4-TBP）。4-TBP广泛存在于工业和消费品中，包括合成皮革、塑料、胶水和杀菌酚类洗涤剂。4-TBP如何导致色素脱失和黑素细胞死亡目前尚不清楚。人黑素细胞的生长有丝分裂原包括α-黑素细胞刺激激素（α-MSH）、碱性成纤维细胞生长因子（bFGF）和12-o-十四酰基佛波醇-13-乙酸酯（TPA）。前两种有丝分裂原是黑素细胞的生理生长因子。我们研究了这些促分裂剂对4-TBP细胞毒性的影响。我们的研究结果表明，从黑素细胞培养物中去除α-MSH或bFGF导致对4-TBP的细胞毒性降低。用已知可被α-MSH激活的cAMP依赖性蛋白激酶A（PKA）抑制剂或酪氨酸激酶bFGF受体抑制剂处理黑素细胞，也获得了类似的结果。相反，从培养基中去除胎牛血清或TPA并不影响黑素细胞对4-TBP的易感性。这些结果表明，cAMP和酪氨酸激酶信号通路的激活，这两者都参与了黑素细胞的促有丝分裂反应，增加了这些细胞对4-TBP的细胞毒性作用的敏感性。
In the search for environmental compounds responsible for contact or occupational vitiligo, it was found that the most potent was 4-tertiary butylphenol (4-TBP). Exposure to 4-TBP is widespread both in industry and in consumer items including synthetic leather, plastic, glues, and germicidal phenolic detergents. How 4-TBP causes depigmentation and the death of melanocytes is currently unclear. Growth mitogens for human melanocytes include α-melanocyte stimulating hormone (α-MSH), basic fibroblast growth factor (bFGF) and 12-o-tetradecanoylphorbol-13-acetate (TPA). The former two mitogens are physiological growth factors for melanocytes. We have studied the effects of these mitogens on the cytotoxicity of 4-TBP in human melanocytes. Our results demonstrated that deprivation of α-MSH or bFGF from melanocyte cultures resulted in reduced cytotoxicity to 4-TBP. Similar results were obtained upon treatment of melanocytes with an inhibitor of cAMP-dependent protein kinase A (PKA), that is known to be activated by α-MSH, or with an inhibitor of the tyrosine kinase bFGF receptor. In contrast, removal of fetal bovine serum or TPA from the culture medium did not influence the susceptibility of melanocytes to 4-TBP. These results suggest that activation of the cAMP and tyrosine kinase signaling pathways, both of which are involved in the mitogenic response of melanocytes, increase the susceptibility of these cells to the cytotoxic effects of 4-TBP.