Micronuclei in humans induced by exposure to low level of ionizing radiation: influence of polymorphisms in DNA repair genes

Angelini, Sabrina; Kumar, Rajiv; Carbone, Fabio; Maffei, Francesca; Forti, Giorgio; Violante, Francesco Saverio; Lodi, Vittorio; Curti, Stefania; Hemminki, Kari; Hrelia, Patrizia

doi:10.1016/j.mrfmmm.2004.10.007

Cited by 99 publications

(78 citation statements)

References 59 publications

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“…Previous studies have shown that IR results in macromolecular ionisation and dissociation, and could directly or indirectly induce DNA damage, damage to leucocyte function and increase the aberration rate of leucomonocytes, leading to increased risk of MN and CAs (29 -31) . Consistent with the results obtained here, Angelini et al have demonstrated that IR may result in a higher frequency of MN and CAs, and lead to significantly higher DNA damage in radiation workers, compared with healthy controls (23) . The United Nations Scientific Committee on the Effects of Atomic Radiation estimated a global value of a mean annual effective dose of 0.5 mSv (UNSCEAR 2008 Report) for the optimisation of protection of occupationally exposed workers (32) .…”

Section: Discussionsupporting

confidence: 93%

“…The results obtained here indicate that the frequencies of MN and CA in workers exposed to IR are significantly higher compared with healthy controls, implying that IR exposure may cause a higher incidence of MN and CA in radiation workers. Owing to its universal applications in diagnostic and therapeutic methods, IR is a major contributor to man-made sources of radiation (23) . IR has negative effects on human health, especially in radiation workers, as reflected by the increase in a variety of peripheral haemograms, MN and CAs (17,24,25) .…”

Section: Discussionmentioning

confidence: 99%

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Effects of Ionising Radiation on Micronucleus Formation and Chromosomal Aberrations in Chinese Radiation Workers

Qin

Cao

Shen

et al. 2015

Radiat Prot Dosimetry

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This study is aimed to investigate the effects of ionising radiation (IR) on micronuclei (MN) formation and chromosome aberrations (CAs) in Chinese radiation workers. The study was conducted using peripheral blood lymphocytes from 1392 radiation workers from Public Hospitals of the city of Tangshan (the exposed group), and 143 healthy individuals as the control group. Fluorescence in situ hybridisation (FISH) was used to detect the unstable and stable nuclear CAs on metaphase. The MN assay was performed using the cytochalasin B method for cytokinesis-block. The MN and CA frequencies were significantly higher in the exposed group than in healthy controls (both p < 0.001). Examination of the incidence rates of MN and CA showed an increasing trend among workers in some occupations compared with the others (all p < 0.05). There were also significant differences in MN and CA rates among workers with different exposure times (all p < 0.05). Stable CA rates demonstrated an increased trend among workers with different exposure times (all p < 0.05), while no significance of unstable CA rates was found among workers with different exposure times (all p < 0.05). Importantly, the frequencies of CA and MN increased among different cumulative radiation dose groups (all p < 0.05). Correlation analysis showed that the frequencies of MN and CA were positively associated with the cumulative radiation dose. Longterm exposure to IR may have harmful effects on the health of radiation workers. The data obtained here show an increased risk of genetic instability that correlated with occupation, exposure time and equivalent dose among Chinese radiation workers.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Effects of Ionising Radiation on Micronucleus Formation and Chromosomal Aberrations in Chinese Radiation Workers

Qin

Cao

Shen

et al. 2015

Radiat Prot Dosimetry

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“…Individuals carrying XRCC3 Met241 have previously been shown to be deficient in DNA repair as attested by an increase in chromosome deletions using an in vitro cytogenetic challenge assay [Au et al, 2003] and by elevated levels of chromosomal translocations [Kiuru et al, 2005] and micronuclei [Angelini et al, 2005] following in vivo radiation exposures. However, although the present finding would appear to provide further support for an influence on DNA repair, the association between the XRCC3 Thr241Met SNP and G 2 radiosensitivity was not confirmed with FBAT analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Polymorphic variation in DNA repair genes has been reported to influence the response to in vitro irradiation as measured by cell cycle delay [Hu et al, 2001], cytogenetic damage [Lunn et al, 2000;Au et al, 2003;Marcon et al, 2003], and DNA single strand break induction and repair using the Comet assay [Aka et al, 2004;Godderis et al, 2004;Rzeszowska-Wolny et al, 2005]. However, whilst variation in DNA repair gene polymorphisms has been reported to influence the in vivo frequencies of micronuclei [Angelini et al, 2005] and unstable chromosome aberrations [Kiuru et al, 2005] following low dose irradiation, no such effect was found when stable translocations were used as the endpoint [Kiuru et al, 2005;Wilding et al, 2005].…”

Section: Introductionmentioning

confidence: 99%

Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G₂chromosomal radiosensitivity

Wilding¹,

Curwen²,

Tawn³

et al. 2006

Environ and Mol Mutagen

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Sixteen candidate polymorphisms (13 SNPs and 3 microsatellites) in nine genes from four DNA repair pathways were examined in 83 subjects, comprising 23 survivors of childhood cancer, their 23 partners, and 37 offspring, all of whom had previously been studied for G 2 chromosomal radiosensitivity. Genotype at the Asp148Glu SNP site in the APEX gene of the base excision repair (BER) pathway was associated with childhood cancer in survivors (P = 0.001, significant even after multiple test adjustment), due to the enhanced frequency of the APEX Asp148 allele among survivors in comparison to that of their partners. Analysis of variance (ANOVA) of G 2 radiosensitivity in the pooled sample, as well as family-based association test (FBAT) of the family-wise data, showed sporadic suggestions of associations between G 2 radiosensitivity and polymorphisms at two sites (the Thr241-Met SNP site in the XRCC3 gene of the homologous recombinational pathway by ANOVA, and the Ser326Cys site in the hOGG1 gene of the BER pathway by FBAT analysis), but neither of these remained significant after multiple-test adjustment. This pilot study provides an intriguing indication that DNA repair gene polymorphisms may underlie cancer susceptibility and variation in radiosensitivity. Environ. Mol. Mutagen. 48:48-57, 2007.

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“…Compared to the wild-type Thr allele, the variant Met allele has been associated with an increased number of micronuclei in peripheral lymphocytes of humans exposed to IR. 46,47 In contrast, Araujo et al have shown that the wild-type Thr and variant Met proteins are functionally equivalent in the HR repair of DSBs, 48 which may explain the lack of association between XRCC3 Thr241Met SNP and glioma risk; however, we cannot at this time rule out the possibility that the genetic interactions between variant XRCC3 and polymorphic alleles of other DNA repair genes lead to a HR defect. Recent evidence indicates that cells carrying the XRCC3 Thr241Met variant are not able to complement the centrosome amplification and to eliminate aberrant cells by apoptosis, suggesting that this variant seems to be associated with cancer susceptibility.…”

Section: Discussionmentioning

confidence: 67%

XRCC3 haplotypes and risk of gliomas in a Chinese population: A hospital‐based case‐control study

Zhou

Liu

Zhang

et al. 2009

Intl Journal of Cancer

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In mammalian cells, X-ray repair cross-complementing group3 (XRCC3) plays an important role in the DNA double-strand breaks (DSBs) repair by homologous recombination. Genetic polymorphisms in the XRCC3 gene may potentially affect the repair of DSBs and thus confer susceptibility to gliomas. In this study, we used a haplotype-based approach to investigate whether 4 tagging single nucleotide polymorphisms of the XRCC3 gene are associated with risk of gliomas in 771 glioma patients and 752 cancerfree controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the unconditional logistic regression, and haplotype associations were estimated using Haplo.Stat. After adjustment for age and sex, the variant G allele of rs861530 and T allele of rs3212092 were significantly associated with an increased risk of gliomas (AG/GG versus AA: adjusted OR 5 1.44, 95% CI 5 1.15-1.80, p 5 0.001 and CT/TT versus CC: adjusted OR 5 1.66, 95% CI 5 1.12-2.46, p 5 0.013, respectively). Consistent with these results, XRCC3 haplotype ''GGCC'' containing rs861530 G allele and haplotype ''AGTC'' containing rs3212092 T allele were also significantly associated with an elevated risk of gliomas compared with the common haplotype ''AGCC'' (adjusted OR 5 1.35, 95% CI 5 1.14-1.58, p 5 0.000 and adjusted OR 5 1.67, 95% CI 5 1.11-2.52, p 5 0.015, respectively). Our results suggest that common genetic variants in the XRCC3 gene may modulate glioma risk. ' 2009 UICC

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Micronuclei in humans induced by exposure to low level of ionizing radiation: influence of polymorphisms in DNA repair genes

Cited by 99 publications

References 59 publications

Effects of Ionising Radiation on Micronucleus Formation and Chromosomal Aberrations in Chinese Radiation Workers

Effects of Ionising Radiation on Micronucleus Formation and Chromosomal Aberrations in Chinese Radiation Workers

Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G₂chromosomal radiosensitivity

XRCC3 haplotypes and risk of gliomas in a Chinese population: A hospital‐based case‐control study

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Micronuclei in humans induced by exposure to low level of ionizing radiation: influence of polymorphisms in DNA repair genes

Cited by 99 publications

References 59 publications

Effects of Ionising Radiation on Micronucleus Formation and Chromosomal Aberrations in Chinese Radiation Workers

Effects of Ionising Radiation on Micronucleus Formation and Chromosomal Aberrations in Chinese Radiation Workers

Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G2chromosomal radiosensitivity

XRCC3 haplotypes and risk of gliomas in a Chinese population: A hospital‐based case‐control study

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Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G₂chromosomal radiosensitivity