Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity

Jennifer Hu, Tasha R. Smith, Mark Steven Miller, Harvey W. Mohrenweiser, Andrea Golden, L. Douglas Case

Research output: Contribution to journalArticle

285 Citations (Scopus)

Abstract

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 G2 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 (X2 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.

Original languageEnglish
Pages (from-to)917-922
Number of pages6
JournalCarcinogenesis
Volume22
Issue number6
StatePublished - Jun 19 2001
Externally publishedYes

Fingerprint

Radiation Tolerance
Amino Acid Substitution
Ionizing Radiation
Exons
Genotype
Viperidae
Genes
Cell Cycle
DNA Repair
DNA-(Apurinic or Apyrimidinic Site) Lyase
Mitotic Index
Codon
Restriction Fragment Length Polymorphisms
Linear Models
Hypersensitivity
Fluorescence
Alleles
X-Rays
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research

Cite this

Hu, J., Smith, T. R., Miller, M. S., Mohrenweiser, H. W., Golden, A., & Case, L. D. (2001). Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity. Carcinogenesis, 22(6), 917-922.

Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity. / Hu, Jennifer; Smith, Tasha R.; Miller, Mark Steven; Mohrenweiser, Harvey W.; Golden, Andrea; Case, L. Douglas.

In: Carcinogenesis, Vol. 22, No. 6, 19.06.2001, p. 917-922.

Research output: Contribution to journalArticle

Hu, J, Smith, TR, Miller, MS, Mohrenweiser, HW, Golden, A & Case, LD 2001, 'Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity', Carcinogenesis, vol. 22, no. 6, pp. 917-922.
Hu J, Smith TR, Miller MS, Mohrenweiser HW, Golden A, Case LD. Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity. Carcinogenesis. 2001 Jun 19;22(6):917-922.
Hu, Jennifer ; Smith, Tasha R. ; Miller, Mark Steven ; Mohrenweiser, Harvey W. ; Golden, Andrea ; Case, L. Douglas. / Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity. In: Carcinogenesis. 2001 ; Vol. 22, No. 6. pp. 917-922.
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abstract = "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 G2 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 (X2 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.",
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