Telomere length modulates human radiation sensitivity in vitro

Castellà, María; Puerto, S.; Creus, A.; Marcos, Ricard; Surrallés, Jordi

doi:10.1016/j.toxlet.2007.05.012

Cited by 44 publications

(30 citation statements)

References 36 publications

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“…These data are in agreement with the notion that the shortest telomere, but not the average telomere length per se has an impact on cellular chromosomal instability [16,40]. In addition, in studies investigating the impact of telomeres on radiosensitivity the role of telomere loss was almost completely neglected, in that either TRF analysis [22,25,26], telomeric q-FISH [14] or f-FISH [23,26,27] were carried out. The mechanism by which telomere loss impact on cell viability is not an issue of the present paper.…”

Section: Discussionsupporting

confidence: 81%

“…The mechanism by which telomere loss impact on cell viability is not an issue of the present paper. However, it should be recalled that besides the classical effect on "stickness" and propagation of chromosomal instability critical for cell viability [7,22,40] telomere shortening/loss is also accompanied by a decreased density of heterochromatic histone marks and hyperacetylation of subtelomeric regions with consequent abnormal gene-expression changes in sub-telomeric genes [37]. Excessive telomere shortening is also responsible for an altered DNA damage response after exposure to ionizing radiations [18].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, primary cells carrying mutations in genes devoted to DNA repair as DNA-PKcs, Ku70, Ku80, NBS1, MRE11, RAD50, ATM, FA, BRCA1 and WRN display accelerated telomere shortening [19][20][21] and increased sensitivity to irradiation. Overall, these studies indicate that an inverse relationship between telomere length and the degree of individual sensitivity to ionizing radiation exists in primary cells with an absent or insufficient level of telomerase [14,[22][23][24]11]. However, it should be pointed out that such a relationship is still a matter of debate, in that controversial data are available in the literature.…”

Section: Introductionmentioning

confidence: 99%

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Telomere loss, not average telomere length, confers radiosensitivity to TK6-irradiated cells

Berardinelli

Nieri

Sgura

et al. 2012

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Telomere loss, not average telomere length, confers radiosensitivity to TK6-irradiated cells

Berardinelli

Nieri

Sgura

et al. 2012

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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“…Fifty-three percent (nZ41) were cured after initial treatment and had no recurrence and 19.5% (nZ15) were cured after further therapies for recurrent disease. Fifteen cured patients (19.5%) were adrenal insufficient at the time of telomere analysis and required substitution therapy with hydrocortisone (mean dose 17.6G3.7 mg and range [10][11][12][13][14][15][16][17][18][19][20]. Nine patients (11.7%) were GH deficient (four of which were replaced with recombinant human GH (rhGH)); eight women (10.4%) were gonadotropin deficient (all on estrogen/progesterone hormone replacement therapy); and 15 patients (19.4%) were hypothyroid, ten due to thyroid-stimulating hormone (TSH) deficiency and five due to primary hypothyroidism (all on L-thyroxine (L-T 4 ) replacement).…”

Section: Subjectsmentioning

confidence: 99%

“…The time elapsed between both analyses was 40.1G15.6 months and mean time of remission was 28.5G14.1 months. Three cured patients (20%) were adrenal insufficient at the time of telomere analysis and required substitution therapy with hydrocortisone (mean dose 18.3G2.2 mg and range [10][11][12][13][14][15][16][17][18][19][20]; four patients (26.6%) were hypothyroid, two due to TSH deficiency and two due to primary hypothyroidism (all on L-T 4 replacement). None of the cured patients were GH-deficient; seven women (46.6%) were postmenopausal at remission, but no gonadotropin deficiency was observed (nZ8).…”

Section: Subjectsmentioning

confidence: 99%

Telomere length analysis in Cushing's syndrome

Aulinas

Ramírez

Barahona

et al. 2014

European Journal of Endocrinology

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Introduction: Hypercortisolism in Cushing's syndrome (CS) is associated with increased morbidity and mortality. Hypercortisolism also occurs in chronic depressive disorders and stress, where telomere length (TL) is shorter than in controls. We hypothesized that shortening of telomere might occur in CS and contribute to premature aging and morbidity. Aim: To investigate TL in CS patients compared with controls. Methods: Seventy-seven CS patients (14 males, 59 pituitary, 17 adrenal, and one ectopic; 21 with active disease) were compared with 77 gender-, age-, and smoking-matched controls. Fifteen CS were evaluated longitudinally, during active disease and after remission of hypercortisolism. Leukocyte TL was measured by telomere restriction fragment-Southern technique. Clinical markers were included in a multiple linear regression analysis to investigate potential predictors of TL. Results: Mean TL in CS patients and controls was similar (7667 vs 7483 bp, NS). After adjustment for age, in the longitudinal evaluation, TL was shorter in active disease than after remission (7273 vs 7870, P!0.05). Age and dyslipidemia were negative predictors (P!0.05), and total leukocyte count was a positive predictor for TL (P!0.05). As expected, a negative correlation was found between TL and age (CS, RZK0.400 and controls, RZK0.292; P!0.05). No correlation was found between circulating cortisol, duration of exposure to hypercortisolism or biochemical cure and TL. Conclusion: Even though in the cross-sectional comparison of CS and controls no difference in TL was found, in the longitudinal evaluation, patients with active CS had shorter TL than after biochemical cure of hypercortisolism. These preliminary results suggest that hypercortisolism might negatively impact telomere maintenance. Larger studies are needed to confirm these findings.

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Genotoxic risk of ethyl-paraben could be related to telomere shortening

Finot¹,

Kaddour

Morat

et al. 2016

J. Appl. Toxicol.

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The ability of parabens to promote the appearance of multiple cancer hallmarks in breast epithelium cells provides grounds for regulatory review of the implication of the presence of parabens in human breast tissue. It is well documented that telomere dysfunction plays a significant role in the initiation of genomic instability during carcinogenesis in human breast cancer. In the present study, we evaluated the genotoxic effect of ethyl 4-hydroxybenzoate (ethyl-paraben), with and without metabolic activation (S9), in studies following OECD guidelines. We observed a significant increase in genotoxic damage using the Mouse Lymphoma Assay and in vitro micronucleus (MN) tests in the L5178Y cell line in the presence of S9 only after a short exposure. A high frequency of MN was observed in the TK6 cells after a short exposure (3 h) in the presence of S9 and a long exposure (26 h) without S9. We found significant increases in the MN frequency and induced chromosomal aberrations in the lymphocytes of only one donor after ethyl-paraben exposure in the presence of S9 after a short exposure. Cytogenetic characterization of the paraben-treated cells demonstrated telomere shortening associated with telomere loss and telomere deletions in L5178Y and TK6 cells and lymphocytes of the paraben sensitive-donor. In a control cohort of 68 human lymphocytes, telomere length and telomere aberrations were age-dependent and showed high inter-individual variation. This study is the first to link telomere shortening and the genotoxic effect of ethyl paraben in the presence of S9 and raises the possibility that telomere shortening may be a proxy for underlying inter-individual sensitivity to ethyl-paraben. Copyright © 2016 John Wiley & Sons, Ltd.

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Telomere length modulates human radiation sensitivity in vitro

Cited by 44 publications

References 36 publications

Telomere loss, not average telomere length, confers radiosensitivity to TK6-irradiated cells

Telomere loss, not average telomere length, confers radiosensitivity to TK6-irradiated cells

Telomere length analysis in Cushing's syndrome

Genotoxic risk of ethyl-paraben could be related to telomere shortening

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