6价铬[Cr(Ⅵ)]是我国一种常见的生产性毒物,广泛用于机械、化工、汽车、冶金、纺织等领域.流行病学调查发现,长期暴露于铬,特别是生产铬酸盐的工人肺癌高发.1990年国际癌症研究所(IARC)认定铬为人类致癌物[1].研究证明,六价铬化合物是最强有力的具基因毒性的铬化合物,对体外培养的细胞具有明显的毒性作用[2,3],但有关Cr(Ⅵ)对细胞内癌基因及抑癌基因表达产物的影响报道较少.为此,本实验采用免疫组织化学方法检测不同浓度重铬酸钾染毒对人胚肺细胞P53和Bcl-2蛋白表达的影响,为深入研究六价铬致癌的分子机制提供基础数据.

Acrylamide (ACR) is a known industrial neurotoxic chemical that can induce neurodegeneration. Cytoskeletal protein aggregation is a pathological hallmark of neurodegenerative disorders. This study was an initial exploration on cytoskeletal proteins in plasma as potential biomarkers of ACR neurotoxicity. Low and high ACR groups received 20 mg/kg and 40 mg/kg ACR by intraperitoneal injection in adult Wistar rats and control group received physiological saline. Rats were all killed after 8 weeks to evaluate the levels of neurofilament(NF)-L, NF-M, NF-H, beta-actin, alpha-tubulin, beta-tubulin, tau, MAP(2) proteins in plasma using both SDS-PAGE and western blotting. Compared with the control, the levels of NF-L, NF-M, NF-H, beta-actin, tau, MAP2 proteins decreased and the level of alpha-tubulin increased in high ACR group, the levels of alpha-tubulin, beta-tubulin and MAP2 increased in low ACR group. The results suggested that the changes of these proteins might be relevant to the neurotoxicity of ACR. Some of the cytoskeletal proteins in plasma might be used as marker of biological effect in ACR induced neuropathy.

六价铬化合物是普遍存在的环境污染物,常用于印染、皮革加工、木材防腐保存、有机合成及某些催化剂的制造等.其毒性大,人体口服六价铬的致死剂量约为1.5～1.6 g,能影响体内氧化、还原代谢,并可与核酸结合引起呼吸道、消化道刺激作用,并有明显的致癌作用.早在1935年,德国的工厂医师Pfeil发现铬酸盐工人肺癌高发,随后美国、英国、德国、日本、前苏联和意大利等国的流行病学调查研究都予以证实.我国20世纪80年代对2545名铬酸盐工人进行回顾性和前瞻性流行病学调查研究,发现肺癌高发,发病率高达82.08/10万,而对照组为22.79/10万.1990年,国际癌症研究中心明确六价铬化合物为人类致癌物(IARC 1990资料).但到目前为止,六价铬的致癌机制仍未完全阐明.本文就六价铬致肺癌的反应机制,从肺癌相关基因调控失常、细胞突变、凋亡等几个方面进行综述.