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TOXICOL IN VITRO :中科院上海生科院冯英研究组阐明塑化剂潜在致癌性的新机制

2017-04-19 冯英 生物帮

2017年4月14日,国际毒理学学术期刊《Toxicology in Vitro》在线发表了中国科学院上海生命科学研究院冯英研究组的最新研究进展“Long-term di (2-ethylhexyl)-phthalate exposure promotes proliferation and survival of HepG2 cells via activation of NFκB”。研究为塑化

2017年4月14日,国际毒理学学术期刊《Toxicology in Vitro》在线发表了中国科学院上海生命科学研究院冯英研究组的最新研究进展“Long-term di (2-ethylhexyl)-phthalate exposure promotes proliferation and survival of HepG2 cells via activation of NFκB”。研究为塑化剂DEHP的致癌可能性提供了新的证据,并揭示了塑化剂可能通过刺激肝癌细胞的炎性反应、激活NFκB信号通路导致癌细胞增殖和生存能力增强。

塑化剂是一种常见的化工原料,与我们的生活密切相关。苯二甲酸酯类是最常见的塑化剂,其中最常被用到的就是di (2-ethylhexyl)-phthalate,也就是DEHP。DEHP不仅被用在多种塑料制品中,同时也在很多粘合剂,橡胶制品,电缆和医疗器械中应用。由于DEHP在很多制品当中是以非共价键形式掺入,导致塑化剂容易从相关制品中渗漏到环境、食品、饮水等当中,形成了困扰我们的环境问题。DEHP的内分泌干扰毒性是比较明确的,但是它的致癌风险目前却存在着比较大的争议。

在冯英研究员的指导下,魏宁博士等为了弄清楚DEHP的致癌风险及其作用机制,在参考人类日常塑化剂暴露剂量的基础上,选用人类的肝癌细胞HepG2作为实验材料,模拟人类日常暴露剂量,对HepG2细胞进行长期刺激处理,观察了DEHP对癌细胞生长生存状态的影响。研究发现长期、极低浓度的DEHP刺激可以促进HepG2细胞的增殖、增强细胞的生存能力。后续的转录组测序分析结果显示:癌细胞在长期的DEHP刺激之后,其细胞内与炎性反应相关的TLR-NFκB信号通路被激活;抑制NFκB信号通路可以消除DEHP促进癌细胞生长以及生存能力的作用,这些均提示DEHP可能通过诱发炎性反应促进癌症的发生。此项研究揭示了塑化剂DEHP在极低的暴露浓度下,可能通过诱发肝癌细胞的炎性反应进而促进肝癌发生的风险性。

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    2017-09-02 zzc2224
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    2018-03-23 gous
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    2017-04-21 jambiya

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