文献类型：期刊文献

英文题名：Formaldehyde induces toxic effects and regulates the expression of damage response genes in BM-MSCs

作者：She, Yali[1,2,3,4];Li, Yi[2,5];Liu, Yongqi[3,4];Asai, Guli[6];Sun, Shaobo[7];He, Jianxin[2,3,4];Pan, Zheng[8];Cui, Yan[1]

第一作者：舍雅莉;She, Yali

通信作者：Cui, Y[1]

机构：[1]Gansu Agr Univ, Coll Vet Med, Lanzhou 730070, Peoples R China;[2]Gansu Univ Tradit Chinese Med, Dept Syst Biol & TCM Transformat, Lanzhou 730000, Peoples R China;[3]Gansu Univ Tradit Chinese Med, Lanzhou 730000, Peoples R China;[4]Gansu Univ Tradit Chinese Med, Key Lab Tradit Chinese Med Pharmacol & Toxicol, Lanzhou 730000, Peoples R China;[5]Lanzhou Univ, Sch Basic Med Sci, Dept Genet, Lanzhou 730000, Peoples R China;[6]Northwest Minor Univ, Sch Med, Lanzhou 730000, Peoples R China;[7]Gansu Univ Tradit Chinese Med, Dept Integrat Med, Lanzhou 730000, Peoples R China;[8]Lanzhou Univ, Hosp 2, Dept Intens Care, Lanzhou 730000, Peoples R China

第一机构：Gansu Agr Univ, Coll Vet Med, Lanzhou 730070, Peoples R China

通信机构：[1]corresponding author), Gansu Agr Univ, Coll Vet Med, Lanzhou 730070, Peoples R China.

年份：2013

卷号：45

期号：12

起止页码：1011

外文期刊名：ACTA BIOCHIMICA ET BIOPHYSICA SINICA

收录：;Scopus(收录号：2-s2.0-84904832887);WOS:【SCI-EXPANDED(收录号:WOS:000328083000004)】；

基金：This work was supported by grants from the National Natural Scientific Foundation of China (81060351/H2810), Research Foundation of Education Bureau of Gansu Province, China (0906-03), and the Science-Technology Foundation for Middle-aged and Young Scientist of the Traditional Chinese Medical College of Gansu, China (09ZQ-2).

语种：英文

外文关键词：comet assay; DNA-protein crosslinks; sister chromatid exchange; micronuclei; PCR array

摘要：In this study, we assessed the toxic effects of formaldehyde (FA) on mouse bone marrow mesenchymal stem cells (BM-MSCs). Cytotoxicity was measured by using MTT assay. DNA strand breakage was detected by standard alkaline comet assay and comet assay modified with proteinase K (PK). DNA-protein crosslinks (DPCs) were detected by KCl-SDS precipitation assay. We found that FA at a concentration from 75 to 200 mu M inhibited cell survival and induced DPCs over 125 mu M. The PK-modified comet assay showed that FA-induced DNA strand breakage was increased in a dose-dependent manner from 75 to 200 mu M. On the other hand, standard alkaline comet assay showed that DNA strand breakage was decreased with FA concentration over 125 mu M. We confirmed by using Pearson correlation that there was a negative linear correlation between DPCs and survival rate (r = -0.987, P < 0.01) and positive linear relationships between DPCs and (i) sister chromatid exchange and (ii) micronucleus (r = 0.995, P < 0.01; r = 0.968, P < 0.01). DNA damage RT2 profiler polymerase chain reaction array was used to investigate the changes in the expression of damage response genes. Xpa and Xpc of the nucleotide excision repair pathway and Brca2, Rad51, and Xrcc2 of the homologous recombination pathway were all up-regulated in both 75 and 125 mu M FA. However, the same genes were down-regulated with 175 mu M FA. The expressions of Chek1 and Hus1, which are involved in cell cycle regulation, were altered in the same manner with 75, 125, and 175 mu M FA. These results indicated that Xpa, Xpc, Brca2, Rad51, Xrcc2, Chek1, and Hus1 were essential for the BM-MSCs to counteract the effects of FA.