Radiation-induced breakpoint misrejoining in human chromosomes: random or non-random?

Kl, Johnson; Dj, Brenner; Nath, J.; Jd, Tucker; Cr, Geard

doi:10.1080/095530099140582

Cited by 48 publications

(21 citation statements)

References 40 publications

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“…''Whole genome equivalent'' refers to the correction factor developed by Lucas et al (38) that is applied to stable aberration frequencies detected by single-color FISH to adjust for those aberrations occurring in chromosomes that are not ''painted'' by the FISH probes and those aberrations involving chromosomes painted with the same color. Application of the correction factor is based on the assumption that the probability of a break(s) occurring in any particular chromosome is dependent on its DNA content; that is, larger chromosomes are subject to more breaks (37,38). Whole genome equivalents for this study were determined by adapting the correction developed by Lucas et al (38) to include the additional paint color used in this study rather than the single-color FISH used by Lucas et al:…”

Section: Exposure Assessmentmentioning

confidence: 99%

Chromosomal Aberrations in Cord Blood Are Associated with Prenatal Exposure to Carcinogenic Polycyclic Aromatic Hydrocarbons

Bocskay¹,

Tang²,

Orjuela³

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

109

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Molecular and traditional epidemiology studies have indicated a possible relationship between in utero environmental exposures and increased risk for childhood cancers, especially acute leukemias. Chromosomal aberrations have been associated with environmental exposures and cancer risk in adults. In order to more clearly define the association between prenatal exposures to carcinogenic polycyclic aromatic hydrocarbons (PAH) and chromosomal aberrations, chromosomal aberration frequencies were measured in a subset of 60 newborns from the Columbia Center for Children's Environmental Health (CCCEH) Prospective Cohort Study. The subset was composed of African American and Dominican, nonsmoking mother-newborn pairs residing in low-income neighborhoods of New York City, who were exposed to varying levels of airborne PAHs. Prenatal exposure was assessed by questionnaire, personal air monitoring during the third trimester, and PAH-DNA adducts in umbilical cord blood. Chromosomal aberrations were measured in cord blood lymphocytes by fluorescence in situ hybridization. PAH-DNA adducts were not associated with chromosomal aberrations. However, airborne PAHs were significantly associated with stable aberration frequencies in cord blood (P < 0.01). Moreover, stable aberration frequencies were significantly higher among African American newborns compared with Dominican, despite no significant differences in PAH exposure. These results show for the first time an association between prenatal exposure to airborne carcinogenic PAHs and chromosomal aberrations in cord blood, suggesting that such prenatal exposures have the potential to cause cytogenetic damage that has been related to increased cancer risk in other populations.

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Section: Exposure Assessmentmentioning

confidence: 99%

Chromosomal Aberrations in Cord Blood Are Associated with Prenatal Exposure to Carcinogenic Polycyclic Aromatic Hydrocarbons

Bocskay¹,

Tang²,

Orjuela³

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

109

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“…It was based on the theory that the probability of an aberrant event occurring in any particular chromosome is determined by its DNA content [Lucas et al, 1992;Tucker et al, 1993]. This theory has been substantiated in some radiation and chromosome aberration studies that have demonstrated a linear relationship between DNA content and breakpoints, i.e., larger chromosomes are subject to more breaks [Puerto et al, 1999b;Johnson et al, 1999;Sachs et al, 2000]. However, multiple studies have demonstrated that chromosome aberrations induced with radiation and chemicals are not randomly distributed by chromosome size [Knehr et al, 1996;Stephan and Pressl, 1997;Barquinero et al, 1998;Smith et al, 1998;Wu et al, 1998;Zhang et al, 1998aZhang et al, ,b, 2005Eastmond et al, 2001;Verdorfer et al, 2001;Zhu et al, 2002;Beskid et al, 2006].…”

Section: Introductionmentioning

confidence: 99%

“…Until the development of FISH, unstable aberrations, detected by Giemsa-staining, were used as an indicator of levels of chromosome breakage. Chromosome breakage was used as a surrogate endpoint for the direct measurement of stable aberrations [Johnson et al, 1998[Johnson et al, , 1999Mitelman, 2000].…”

Section: Introductionmentioning

confidence: 99%

Fluorescence in situ hybridization is necessary to detect an association between chromosome aberrations and polycyclic aromatic hydrocarbon exposure in utero and reveals nonrandom chromosome involvement

Bocskay

Orjuela

Tang

et al. 2007

Environ and Mol Mutagen

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Chromosome aberrations are associated with environmental exposures in infants and children. Recently we reported that prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAHs) was significantly (P < 0.01) associated with stable aberration frequencies in cord blood from a subset of 60 newborns from the Columbia Center for Children's Environmental Health Prospective Cohort Study (Bocskay K et al. [2005]: Cancer Epidemiol Biomarkers Prev 14:506-511). To determine whether the environmental exposures may be targeting specific chromosomes and to compare various methods for measuring chromosome aberrations, we further evaluated this same subset of subjects composed of African-American and Dominican nonsmoking mother-newborn pairs residing in low-income neighborhoods of New York City, and exposed to varying levels of airborne PAHs. Chromosome aberrations were measured in cord blood lymphocytes, both by whole chromosome probe (WCP) fluorescence in situ hybridization (FISH) and traditional Giemsa-staining. Prenatal exposures were assessed by personal air monitoring. Breaks in chromosomes 1-6, as detected by WCP FISH, were nonrandomly distributed, underscoring the importance of appropriate chromosome probe selection to capture cytogenetic damage in response to exposure. FISH for stable aberrations was found to be a more sensitive method for detecting aberration frequencies associated with environmental exposures, when compared with FISH for unstable aberrations or Giemsa-staining for aberrations. Together, these results suggest that PAHs may be targeting specific chromosomes and highlight the importance of using the more sensitive detection methods to assess risk in populations with low levels of exposure.

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“…PTC1 and PTC3 rearrangements have also been induced in vitro and in vivo by irradiation of tumor cell lines and fetal thyroid tissue that had previously been transplanted into severe combined immunodeficient (SCID) mice (15)(16)(17). Several studies suggest that different kinds of radiation (UVA and ionizing radiation) induce a nonrandom distribution of the DNA lesions across the whole genome (18,19).…”

Section: Introductionmentioning

confidence: 99%

Enhanced Sensitivity of the RET Proto-Oncogene to Ionizing Radiation In vitro

Volpato

Martínez-Alfaro²,

Corvi³

et al. 2008

Cancer Research

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Exposure to ionizing radiation is a well-known risk factor for a number of human cancers, including leukemia and thyroid cancer. It has been known for a long time that exposure of cells to radiation results in extensive DNA damage; however, a small number of studies have tried to explain the mechanisms of radiation-induced carcinogenesis. The high prevalence of RET/PTC rearrangements in patients who have received external radiation, and the evidence of in vitro induction of RET rearrangements in human cells, suggest an enhanced sensitivity of the RET genomic region to damage by ionizing radiation. To assess whether RET is indeed more sensitive to radiations than other genomic regions, we used a COMET assay coupled with fluorescence in situ hybridization, which allows the measurement of DNA fragmentation in defined genomic regions of single cells. We compared the initial DNA damage of the genomic regions of RET, CXCL12/SDF1, ABL, MYC, PLA2G2A, p53, and JAK2 induced by ionizing radiation in both a lymphoblastoid and a fetal thyroid cell line. In both cell lines, RET fragmentation was significantly higher than in other genomic regions. Moreover, a differential distribution of signals within the COMET was associated with a higher percentage of RET fragments in the tail. RET was more susceptible to fragmentation in the thyroid-derived cells than in lymphoblasts. This enhanced susceptibility of RET to ionizing radiation suggests the possibility of using it as a radiation exposure marker. [Cancer Res 2008;68(21):8986-92]

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Radiation-induced breakpoint misrejoining in human chromosomes: random or non-random?

Cited by 48 publications

References 40 publications

Chromosomal Aberrations in Cord Blood Are Associated with Prenatal Exposure to Carcinogenic Polycyclic Aromatic Hydrocarbons

Chromosomal Aberrations in Cord Blood Are Associated with Prenatal Exposure to Carcinogenic Polycyclic Aromatic Hydrocarbons

Fluorescence in situ hybridization is necessary to detect an association between chromosome aberrations and polycyclic aromatic hydrocarbon exposure in utero and reveals nonrandom chromosome involvement

Enhanced Sensitivity of the RET Proto-Oncogene to Ionizing Radiation In vitro

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