title: Modulation of DNA repair capacity by ataxia telangiectasia mutated gene polymorphisms among polycyclic aromatic hydrocarbons-exposed workers.
abstract: The purpose of this study was to address the association between the ataxia telangiectasia mutated (ATM) gene polymorphisms and susceptibility to DNA repair capacity (DRC) among polycyclic aromatic hydrocarbons (PAHs)-exposed workers. Polymorphisms of ATM were genotyped. DRC was determined by comet assay. Chromosomal damage was detected by cytokinesis-block micronucleus (CBMN) assay. Flow cytometry was used to detect the distributions of cell cycle. Expressions of ATM and rH2AX were determined by immunoblotting analysis. Luciferase assays were performed to determine the functional difference of ATM promoter region allele. Subjects carrying T allele of rs228589 had significantly lower DRC compared with those with AA genotype. Subjects carrying G allele of rs652311 had significantly lower DRC than those with zero copy number of haplotype CGGT. SH ataxia telangiectasia mutated (SHATM) cells had significantly lower DRC than SH green fluorescent protein (SHGFP) cells induced by bleomycin and higher CBMN frequencies treated by benzo(a)pyrene [B(a)P] than SHGFP cells. After B(a)P treatment, a decrease in the percentage of G1 phase cells was observed in SHATM cells compared with SHGFP cells, rH2AX expressions were increased in SHATM cells and SHGFP cells, but ATM expressions had no change in 16HBE-SHGFP cells and HEK-SHGFP cells. Luciferase expression was not different between rs228589T and rs228589A plasmid constructs. In conclusions, it is suggested that ATM polymorphisms are associated with DRC among PAHs-exposed workers and ATM plays key roles in repair of chromosomal damage and cell cycle control with the treatment of B(a)P.
authors.affiliation: Key Laboratory of Chemical Safety and Health, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, P. R. China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Cheng
authors.forename: Daochuan
authors.initials: D
authors.lastname: Li
authors.forename: Huawei
authors.initials: H
authors.lastname: Duan
authors.forename: Haijun
authors.initials: H
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Bin
authors.forename: Yufei
authors.initials: Y
authors.lastname: Dai
authors.forename: Chuanfeng
authors.initials: C
authors.lastname: Huang
authors.forename: Xuemiao
authors.initials: X
authors.lastname: Liang
authors.forename: Shuguang
authors.initials: S
authors.lastname: Leng
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000395:Air Pollutants, Occupational / Q000633:toxicity* / Q000652:urine; D064007:Ataxia Telangiectasia Mutated Proteins; D016022:Case-Control Studies; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics*; D002460:Cell Line; D002681:China; D020552:Comet Assay; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005838:Genotype; D006801:Humans; D015151:Immunoblotting; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D015162:Micronucleus Tests; D016273:Occupational Exposure / Q000009:adverse effects* / Q000032:analysis; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity* / Q000652:urine; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D000395:Air Pollutants, Occupational; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011084:Polycyclic Aromatic Hydrocarbons; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases