Cr(VI)对人胚肺细胞p53及抑癌基因p21(WAF1)表达的影响

Effect of Cr(VI) on the expression of p53 and WAF1 gene in human embryo lung cell

目的研究人类致癌物Ｃｒ（ＶＩ）对抑癌基因ｐ５３及其下游的抑癌基因ｐ２１（ＷＡＦ１）在多阶段致癌中的作用。方法采用Ｎｏｒｔｈｅｒｎ杂交技术，观察不同浓度Ｋ２Ｃｒ２Ｏ７对人胚肺细胞内ｐ５３及ＷＡＦ１表达的影响。结果Ｃｒ（ＶＩ）对ｐ５３表达的影响呈双相作用，０～１．２５０μｍｏｌ／Ｌ范围内Ｋ２Ｃｒ２Ｏ７抑制ｐ５３的表达；１．２５０～５．０００μｍｏｌ／ＬＫ２Ｃｒ２Ｏ７可刺激ｐ５３的表达。ＷＡＦ１的变化趋势与ｐ５３相一致，即１．２５０μｍｏｌ／ＬＫ２Ｃｒ２Ｏ７可明显抑制ＷＡＦ１的表达，而随着Ｋ２Ｃｒ２Ｏ７浓度的增加，ＷＡＦ１的表达也呈升高趋势。结论低剂量Ｋ２Ｃｒ２Ｏ７影响下的ｐ５３及ＷＡＦ１的低表达可能在Ｃｒ（ＶＩ）多阶段致癌中起重要作用。

Objective To investigate the role of wild type(wt)p53 and WAF1 gene(a down stream gene of p53) in the process of chromium(VI) induced multistage carcinogenesis. Methods Expressions of (wt)p53 and WAF1 in human embryo lung(HEL) cells were analysed at mRNA level using Northern blotting technique. Results Cr(VI) could inhibit the expression of (wt)p53 significantly at the dose of 1.250 μmol/L for 24 h and the changes of WAF1 expression were paralleled with that of (wt)p53.However,the overexpression of (wt)p53 and WAF1 were observed with the increase of doses of K 2Cr 2O 7. Conclusion Because (wt)p53 and WAF1 gene are important in the process of repair of DNA damage and elimination of cells with unrepaired DNA damage,the low expression of p53 and WAF1 gene in HEL cells treated with K 2Cr 2O 7 below 1.250 μmol/L might be one of the mechanism of chromate induced multistage carcinogenesis.