High frequencies of telomeric associations, chromosome aberrations, and sister chromatid exchanges in ulcerative colitis

Cottliar, Alejandra; Fundia, Ariela; Boerr, Luis A.; Sambuelli, Alicia M.; Negreira, Silvia; Gil, Aníbal H.; Gómez, Juan Carlos; Chopita, N; Bernedo, Alberto; Slavutsky, Irma

doi:10.1111/j.1572-0241.2000.02315.x

Cited by 30 publications

(9 citation statements)

References 42 publications

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“…A possible explanation includes a systemic defect, backed by genomic instability and high frequency of telomeric associations in circulating lymphocytes of UC patients. 67 Additional striking differences were detected when LPT division was analysed by CFDA staining. Regardless of CD2 or CD3 activation, CD LPT vigorously expanded while T cell division was drastically restricted in UC, with less than half of the cells dividing.…”

Section: Discussionmentioning

confidence: 97%

Divergent cell cycle kinetics underlie the distinct functional capacity of mucosal T cells in Crohn's disease and ulcerative colitis

Sturm

Leite

Danese

et al. 2004

Gut

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Background: Different abnormalities of T cell effector function distinguish Crohn's disease (CD) from ulcerative colitis (UC). Because cell cycling determines effector function, pathogenic events in CD and UC may depend on cell cycle changes unique to each condition. Methods: Cell cycle kinetics, cycle regulatory molecule expression, apoptosis, caspase and telomerase activity, and cellular expansion were evaluated in CD2 and CD3 activated control, CD, and UC lamina propria T cells. Results: Compared with normal cells, CD T cells cycle faster, express increased phosphorylated Rb and decreased phosphorylated p53 levels, display less caspase activity but more telomerase activity, die less, and undergo vigorous cellular expansion. In contrast, UC T cells cycle slower, express normal levels of phosphorylated Rb and p53, display more caspase activity but have no telomerase activity, die more, and have a limited capacity to expand. Conclusions: T cell cycle abnormalities in CD indicate a state of hyperreactivity compatible with loss of tolerance, but a hyporeactive state compatible with anergy in UC. Thus distinct and divergent T cell cycle characteristics underlie the pathogenesis of the two main forms of inflammatory bowel disease.

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Section: Discussionmentioning

confidence: 97%

Divergent cell cycle kinetics underlie the distinct functional capacity of mucosal T cells in Crohn's disease and ulcerative colitis

Sturm

Leite

Danese

et al. 2004

Gut

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“…Higher frequencies of chromosomal rearrangements and telomere fusions have also been observed in peripheral blood lymphocytes (PBLs) in UC 14 . This may indicate a global predisposition towards genomic instability in IBD, which could represent a biomarker for increased cancer risk, as has been observed in several other malignant and premalignant diseases, 15–20 including colon cancer 21 and celiac disease 22 .…”

Section: Introductionmentioning

confidence: 84%

Lymphocyte telomere dynamics and telomerase activity in inflammatory bowel disease: effect of drugs and smoking

Getliffe

Dulaimi

Martin‐Ruiz³

et al. 2005

Aliment Pharmacol Ther

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SUMMARYBackground: The chromosome instability observed in peripheral blood lymphocytes in ulcerative colitis could be a biomarker of cancer susceptibility. Aim: To determine whether accelerated telomere shortening could explain chromosome instability and assess the effect of drugs and smoking on telomere dynamics in these cells. Methods: Peripheral blood lymphocytes were isolated from ulcerative colitis, Crohn's disease and noninflammatory bowel disease control patients. Telomere lengths were measured by quantitative real-time polymerase chain reaction. After activation and cell separation, telomerase activity and human telomerase reverse transcriptase messenger ribonucleic acid were measured by telomerase repeat amplification protocol enzyme-linked immunosorbent serological assay and

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“…No studies have been conducted on MN formation in the lymphocytes of patients with UC. However there is one available study which is concerned with sister chromatid exchange (SCE) in lymphocytes, where it was reported that SCE was elevated in the lymphocytes of patients with UC [34]. SCE is another cytological method used to detect chromosomal damage.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Genome Instability in Exfoliated Colonic Epithelial Cells and in Mitogen-Stimulated Lymphocytes of Patients with Ulcerative Colitis

Karaman

Hamurcu²,

Dönmez³

et al. 2012

Digestion

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Objective: The present study aimed to evaluate the micronucleus (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in the mitogen-stimulated lymphocytes of patients with ulcerative colitis (UC). In addition, we assessed MN frequency in exfoliated colonic epithelial cells obtained from both the diseased and healthy colonic mucosa of patients. Design: The study was conducted in 22 newly diagnosed patients with UC and in 22 healthy controls. MN, NPB and NBUD values scored in binucleated (BN) cells were obtained from the mitogen-stimulated lymphocytes of patients and control subjects. In addition, the MN values in exfoliated epithelial cells obtained from the diseased and healthy colonic mucosa of patients were evaluated. Results: We found significantly higher MN, NPB and NBUD frequencies in the BN cells of patients with UC than in those of the control subjects (1.61 ± 0.75 vs. 0.89 ± 0.29, 3.93 ± 1.91 vs. 1.39 ± 1.10, and 1.55 ± 0.89 vs. 0.64 ± 0.48, p = 0.001). Also, a statistically significant difference was found between MN frequencies obtained from the diseased and healthy colonic mucosa of patients (1.07 ± 0.46 vs. 0.59 ± 0.21, p = 0.001). No significant relationship was found between age and MN frequency in patients with UC (r = 0.076, p = 0.735). Conclusion: Increased MN, NPB and NBUD frequencies observed in both the lymphocytes and exfoliated colonic epithelial cells obtained from patients with UC may reflect genomic instability.

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High frequencies of telomeric associations, chromosome aberrations, and sister chromatid exchanges in ulcerative colitis

Abstract: Our results demonstrate the presence of an unstable genome in UC patients that could be related to the cancer development observed in this disease.

Cited by 30 publications

References 42 publications

Divergent cell cycle kinetics underlie the distinct functional capacity of mucosal T cells in Crohn's disease and ulcerative colitis

Divergent cell cycle kinetics underlie the distinct functional capacity of mucosal T cells in Crohn's disease and ulcerative colitis

Lymphocyte telomere dynamics and telomerase activity in inflammatory bowel disease: effect of drugs and smoking

Investigation of Genome Instability in Exfoliated Colonic Epithelial Cells and in Mitogen-Stimulated Lymphocytes of Patients with Ulcerative Colitis

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