Gao Ya-Juan, Xiao Cheng-Feng, Chen Sheng, Wang Rui-Bo, He Han-Zhen, Tanguay Robert M, Wu Tang-Chun
Institute of Occupational Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Biomed Environ Sci. 2004 Jun;17(2):144-52.
Benzo[a]pyrene (B[a]P), a ubiquitous environmental pollutant, is a potent procarcinogen and mutagen that can elicit tumors, leading to malignancy. Heat shock proteins (Hsp) have been shown to protect cells against damages caused by various stresses including exposure to numerous chemicals. Whether Hsps, or more specifically Hsp70, are involved in repair of B[a]P-induced DNA damage is currently unknown.
We assessed the potential role of the inducible form of Hsp70 in B[a]P-induced DNA damage of human embryonic lung (HEL) cells using immunoblot and the comet assay (i.e., the single cell gel electrophoresis assay).
Exposure to B[a]P induced a dose-dependent decrease in the level of Hsp70, but a dose-dependent +-increase in DNA damage both in untreated (control) HEL cells and in cells preconditioned by a heat treatment. Heat preconditioning prior to B[a]P exposure potentiated the effect of B[a]P at a low dose (10 micromol/L), but appeared to be protective at higher doses. There was a negative correlation between Hsp70 level and DNA damage in the non-preheated as well as in the preconditioned cells.
These data suggest that exposure of HEL cells to B[a]P may induce a dose-dependent reduction in the levels of the inducible Hsp70. The detailed mechanisms for the reduction of Hsp70 levels by B[a]P and the role of Hsp70 in DNA damage under different concentrations of B[a]P remains to be determined.
苯并[a]芘(B[a]P)是一种普遍存在的环境污染物,是一种强效的前致癌物和诱变剂,可引发肿瘤,导致恶性肿瘤。热休克蛋白(Hsp)已被证明能保护细胞免受包括接触多种化学物质在内的各种应激所造成的损害。目前尚不清楚热休克蛋白,或更具体地说热休克蛋白70(Hsp70)是否参与B[a]P诱导的DNA损伤修复。
我们使用免疫印迹和彗星试验(即单细胞凝胶电泳试验)评估了诱导型Hsp70在B[a]P诱导的人胚肺(HEL)细胞DNA损伤中的潜在作用。
暴露于B[a]P会导致Hsp70水平呈剂量依赖性下降,但在未处理的(对照)HEL细胞和经热处理预处理的细胞中,DNA损伤均呈剂量依赖性增加。在B[a]P暴露前进行热预处理,在低剂量(10微摩尔/升)时增强了B[a]P的作用,但在高剂量时似乎具有保护作用。在未预热以及预处理的细胞中,Hsp70水平与DNA损伤之间存在负相关。
这些数据表明,HEL细胞暴露于B[a]P可能会导致诱导型Hsp70水平呈剂量依赖性降低。B[a]P降低Hsp70水平的详细机制以及Hsp70在不同浓度B[a]P下对DNA损伤的作用仍有待确定。