title: Genetic polymorphisms in 19q13.3 genes associated with alteration of repair capacity to BPDE-DNA adducts in primary cultured lymphocytes.
abstract: Benzo[a]pyrene(B[a]P), and its ultimate metabolite Benzo[a]pyrene 7,8-diol 9,10-epoxide (BPDE), are classic DNA damaging carcinogens. DNA damage in cells caused by BPDE is normally repaired by Nucleotide Excision Repair (NER) and Base Excision Repair (BER). Genetic variations in NER and BER can change individual DNA repair capacity to DNA damage induced by BPDE. In the present study we determined the number of in vitro induced BPDE-DNA adducts in lymphocytes, to reflect individual susceptibility to Polycyclic aromatic hydrocarbons (PAHs)-induced carcinogenesis. The BPDE-DNA adduct level in lymphocytes were assessed by high performance liquid chromatography (HPLC) in 281 randomly selected participants. We genotyped for 9 single nucleotide polymorphisms (SNPs) in genes involved in NER (XPB rs4150441, XPC rs2228001, rs2279017 and XPF rs4781560), BER (XRCC1 rs25487, rs25489 and rs1799782) and genes located on chromosome 19q13.2-3 (PPP1R13L rs1005165 and CAST rs967591). We found that 3 polymorphisms in chromosome 19q13.2-3 were associated with lower levels of BPDE-DNA adducts (MinorT allele in XRCC1 rs1799782, minor T allele in PPP1R13L rs1005165 and minor A allele in CAST rs967571). In addition, a modified comet assay was performed to further confirm the above conclusions. We found both minor T allele in PPP1R13L rs1005165 and minor A allele in CAST rs967571 were associated with the lower levels of BPDE-adducts. Our data suggested that the variant genotypes of genes in chromosome 19q13.2-3 are associated with the alteration of repair efficiency to DNA damage caused by Benzo[a]pyrene, and may contribute to enhance predictive value for individual's DNA repair capacity in response to environmental carcinogens.
authors.affiliation: Dept. of Toxicology, School of Public Health, China Medical University, Shenyang, PR China.
authors.forename: Mingyang
authors.initials: M
authors.lastname: Xiao
authors.affiliation: Dept. of Toxicology, School of Public Health, China Medical University, Shenyang, PR China.
authors.forename: Sha
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Dept. Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Tahar van der
authors.initials: TV
authors.lastname: Straaten
authors.affiliation: Dept. of Toxicology, School of Public Health, China Medical University, Shenyang, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xue
authors.affiliation: Dept. of Toxicology, School of Public Health, China Medical University, Shenyang, PR China.
authors.forename: Guopei
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Dept. of Toxicology, School of Public Health, China Medical University, Shenyang, PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Dept. of Toxicology, School of Public Health, China Medical University, Shenyang, PR China.
authors.forename: Qianye
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Dept. of Toxicology, School of Public Health, China Medical University, Shenyang, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Dept. of Toxicology, School of Public Health, China Medical University, Shenyang, PR China.
authors.forename: Cuihong
authors.initials: C
authors.lastname: Jin
authors.affiliation: Dept. of Toxicology, School of Public Health, China Medical University, Shenyang, PR China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yang
authors.affiliation: Dept. of Toxicology, School of Public Health, China Medical University, Shenyang, PR China.
authors.forename: Shengwen
authors.initials: S
authors.lastname: Wu
authors.affiliation: Dept. of Toxicology, School of Public Health, China Medical University, Shenyang, PR China.
authors.forename: Guolian
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Dept. of Toxicology, School of Public Health, China Medical University, Shenyang, PR China. Electronic address: xiaobo-lu@163.com.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Lu
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D000328:Adult; D000368:Aged; D000483:Alleles; D001564:Benzo(a)pyrene / Q000633:toxicity; D002274:Carcinogens, Environmental / Q000633:toxicity; D002478:Cells, Cultured; D002888:Chromosomes, Human, Pair 19 / Q000187:drug effects / Q000235:genetics*; D020552:Comet Assay / Q000379:methods; D004247:DNA / Q000235:genetics; D018736:DNA Adducts / Q000235:genetics*; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D002274:Carcinogens, Environmental; D018736:DNA Adducts; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D004247:DNA
keywords: Benzo[a]pyrene 7,8-diol 9,10-epoxide(BPDE); CAST; DNA repair capacity; PPP1R13L; Single nucleotide polymorphisms (SNPS)