Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity
Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity
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DOI：
10.1093/carcin/22.6.917
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发表时间：
2001-06-01
期刊：
影响因子：
4.7
通讯作者：
Case, LD
中科院分区：
文献类型：
--
作者：
Hu, JJ;Smith, TR;Case, LD
虽然已经发现了几种DNA修复基因的变体，但它们的功能意义尚未确定。本研究利用从135名无癌女性中收集的样本，通过延长细胞周期Gz延迟来评估DNA修复基因的氨基酸替代变异是否有助于电离辐射（IR）敏感性。采用聚合酶链反应-限制性片段长度多态性（RFLP）测定四种基因型：x射线修复交叉补充组1 (XRCC1外显子6 C / T 194参数/ Trp和外显子10 G / A, 399参数/ Gln), XRCC组3 (XRCC3外显子7 C / T 241刺/满足)和apurinic / apyrimidinic核酸内切酶1 (APE1外显子5 T / G, 148 Asp / Glu), Fluorescence-activated细胞分选仪(流式细胞仪)分析是用来测量细胞周期延迟,APE1(外显子5)与有丝分裂相关基因型明显延迟(P = 0.01), Glu / Glu基因型相比其他两个基因型有长时间的推迟。APE1密码子148 Asp/Asp、Asp/Glu和Glu/Glu基因型女性的有丝分裂延迟指数（平均+/- SD）分别为30.95 +/- 10.15 （n = 49）、30.65 +/- 10.4 （n = 60）和39.56 +/- 13.12 (n = 21)，家族史（FH）与APE1（外显子5）基因型（P = 0.007）以及FH和XRCC1（外显子10）基因型（P = 0.005）在有丝分裂延迟中存在显著交互作用。在四水平模型中评估APE1、Asp148Glu和XRCC1、Arg399Gln基因型时，细胞周期延迟延长与变异等位基因数量显著相关(chi(2)为线性趋势10.9；P = 0.001)，这些结果表明XRCC1和APE1的氨基酸替代变异可能与IR超敏反应有关。
Although several variants of DNA repair genes have been identified, their functional significance has not been determined. Using samples collected from 135 cancer-free women, this study evaluated whether amino acid substitution variants of DNA repair genes contribute to ionizing radiation (IR) susceptibility as measured by prolonged cell cycle Gz delay. PCR-restriction fragment length polymorphism (RFLP) assays were used to determine four genotypes: X-ray repair cross complementing group 1 (XRCC1, exon 6, C/T, 194 Arg/Trp and exon 10, G/A, 399 Arg/Gln), XRCC group 3 (XRCC3, exon 7, C/T, 241 Thr/Met) and apurinic/apyrimidinic endonuclease 1 (APE1, exon 5, T/G, 148 Asp/Glu), Fluorescence-activated cell sorter (FACS) analysis was used to measure cell cycle delay, APE1 (exon 5) genotype was significantly associated with mitotic delay (P = 0.01), with the Glu/Glu genotype having prolonged delay compared with the other two genotypes. The mitotic delay index (mean +/- SD) in women with the APE1 codon 148 Asp/Asp, Asp/Glu and Glu/Glu genotypes was 30.95 +/- 10.15 (n = 49), 30.65 +/- 10.4 (n = 60) and 39.56 +/- 13.12 (n = 21), respectively, There was a significant interaction between family history (FH) and APE1 (exon 5) genotype (P = 0.007) as well as FH and XRCC1 (exon 10) genotype (P = 0.005) in mitotic delay, Lastly, prolonged cell cycle delay was significantly associated with number of variant alleles when APE1 Asp148Glu and XRCC1 Arg399Gln genotypes were evaluated in a four-level model (chi (2) for linear trend 10.9; P = 0.001), These results suggest that amino acid substitution variants of XRCC1 and APE1 may contribute to IR hypersensitivity.