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Genomic instability and cellular stress in organ biopsies and peripheral blood lymphocytes from patients with colorectal cancer and predisposing pathologies.

Lombardi S, Fuoco I, di Fluri G, Costa F, Ricchiuti A, Biondi G, Nardini V, Scarpato R - Oncotarget (2015)

Bottom Line: Genomic instability is a cancer hallmark and is connected to changes in chromosomal structure, often caused by double strand break formation (DSB), and aneuploidy.Colorectal tissues lost GSTO1 expression but increased nuclear localization with pathology progression.Evaluation of genomic damage and cellular stress in colorectal pathologies may facilitate prevention and management of CRC.

View Article: PubMed Central - PubMed

Affiliation: Unità di Genetica, Dipartimento di Biologia, University of Pisa, Pisa, Italy.

ABSTRACT
Inflammatory bowel disease (IBD) and polyps, are common colorectal pathologies in western society and are risk factors for development of colorectal cancer (CRC). Genomic instability is a cancer hallmark and is connected to changes in chromosomal structure, often caused by double strand break formation (DSB), and aneuploidy. Cellular stress, may contribute to genomic instability. In colorectal biopsies and peripheral blood lymphocytes of patients with IBD, polyps and CRC, we evaluated 1) genomic instability using the γH2AX assay as marker of DSB and micronuclei in mononuclear lymphocytes kept under cytodieresis inhibition, and 2) cellular stress through expression and cellular localization of glutathione-S-transferase omega 1 (GSTO1). Colon biopsies showed γH2AX increase starting from polyps, while lymphocytes already from IBD. Micronuclei frequency began to rise in lymphocytes of subjects with polyps, suggesting a systemic genomic instability condition. Colorectal tissues lost GSTO1 expression but increased nuclear localization with pathology progression. Lymphocytes did not change GSTO1 expression and localization until CRC formation, where enzyme expression was increased. We propose that the growing genomic instability found in our patients is connected with the alteration of cellular environment. Evaluation of genomic damage and cellular stress in colorectal pathologies may facilitate prevention and management of CRC.

No MeSH data available.


Related in: MedlinePlus

MNmono resultsPanel A. percentage of mononucleated lymphocytes bearing a micronucleus. ** or a, b and c indicate a significant difference (P < 0.001) from healthy subjects or from IBD, polyps and CRC patients, respectively. In each group, bars represent the mean ± SE Panel B: photos of lymphocytes (Giemsa staining), without micronucleus (1) and with a MN (2). 400x magnification.
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Figure 5: MNmono resultsPanel A. percentage of mononucleated lymphocytes bearing a micronucleus. ** or a, b and c indicate a significant difference (P < 0.001) from healthy subjects or from IBD, polyps and CRC patients, respectively. In each group, bars represent the mean ± SE Panel B: photos of lymphocytes (Giemsa staining), without micronucleus (1) and with a MN (2). 400x magnification.

Mentions: Under forced cytodieresis inhibition condition, MN frequencies in mononucleated cells are 0.39 ± 0.08% and 0.18 ± 0.02% in healthy and IBD subjects, respectively, these values being not different from each other. In the polyp group, we observed a significant increase in the level of MN (0.65 ± 0.08%, P < 0.001) which doubles in the lymphocytes from CRC patients (1.12 ± 0.10%, P < 0.001 vs. healthy donors and IBD, P < 0.01 vs. polyps) (Figure 5A). Sex and age did not produce any effect on data variability.


Genomic instability and cellular stress in organ biopsies and peripheral blood lymphocytes from patients with colorectal cancer and predisposing pathologies.

Lombardi S, Fuoco I, di Fluri G, Costa F, Ricchiuti A, Biondi G, Nardini V, Scarpato R - Oncotarget (2015)

MNmono resultsPanel A. percentage of mononucleated lymphocytes bearing a micronucleus. ** or a, b and c indicate a significant difference (P < 0.001) from healthy subjects or from IBD, polyps and CRC patients, respectively. In each group, bars represent the mean ± SE Panel B: photos of lymphocytes (Giemsa staining), without micronucleus (1) and with a MN (2). 400x magnification.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4558120&req=5

Figure 5: MNmono resultsPanel A. percentage of mononucleated lymphocytes bearing a micronucleus. ** or a, b and c indicate a significant difference (P < 0.001) from healthy subjects or from IBD, polyps and CRC patients, respectively. In each group, bars represent the mean ± SE Panel B: photos of lymphocytes (Giemsa staining), without micronucleus (1) and with a MN (2). 400x magnification.
Mentions: Under forced cytodieresis inhibition condition, MN frequencies in mononucleated cells are 0.39 ± 0.08% and 0.18 ± 0.02% in healthy and IBD subjects, respectively, these values being not different from each other. In the polyp group, we observed a significant increase in the level of MN (0.65 ± 0.08%, P < 0.001) which doubles in the lymphocytes from CRC patients (1.12 ± 0.10%, P < 0.001 vs. healthy donors and IBD, P < 0.01 vs. polyps) (Figure 5A). Sex and age did not produce any effect on data variability.

Bottom Line: Genomic instability is a cancer hallmark and is connected to changes in chromosomal structure, often caused by double strand break formation (DSB), and aneuploidy.Colorectal tissues lost GSTO1 expression but increased nuclear localization with pathology progression.Evaluation of genomic damage and cellular stress in colorectal pathologies may facilitate prevention and management of CRC.

View Article: PubMed Central - PubMed

Affiliation: Unità di Genetica, Dipartimento di Biologia, University of Pisa, Pisa, Italy.

ABSTRACT
Inflammatory bowel disease (IBD) and polyps, are common colorectal pathologies in western society and are risk factors for development of colorectal cancer (CRC). Genomic instability is a cancer hallmark and is connected to changes in chromosomal structure, often caused by double strand break formation (DSB), and aneuploidy. Cellular stress, may contribute to genomic instability. In colorectal biopsies and peripheral blood lymphocytes of patients with IBD, polyps and CRC, we evaluated 1) genomic instability using the γH2AX assay as marker of DSB and micronuclei in mononuclear lymphocytes kept under cytodieresis inhibition, and 2) cellular stress through expression and cellular localization of glutathione-S-transferase omega 1 (GSTO1). Colon biopsies showed γH2AX increase starting from polyps, while lymphocytes already from IBD. Micronuclei frequency began to rise in lymphocytes of subjects with polyps, suggesting a systemic genomic instability condition. Colorectal tissues lost GSTO1 expression but increased nuclear localization with pathology progression. Lymphocytes did not change GSTO1 expression and localization until CRC formation, where enzyme expression was increased. We propose that the growing genomic instability found in our patients is connected with the alteration of cellular environment. Evaluation of genomic damage and cellular stress in colorectal pathologies may facilitate prevention and management of CRC.

No MeSH data available.


Related in: MedlinePlus