title: Genomic instability and cellular stress in organ biopsies and peripheral blood lymphocytes from patients with colorectal cancer and predisposing pathologies.
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.
authors.affiliation: Unità di Genetica, Dipartimento di Biologia, University of Pisa, Pisa, Italy.|Research Center Nutraceuticals and Food for Health-Nutrafood, University of Pisa, Pisa, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Lombardi
authors.affiliation: Unità di Genetica, Dipartimento di Biologia, University of Pisa, Pisa, Italy.|Research Center Nutraceuticals and Food for Health-Nutrafood, University of Pisa, Pisa, Italy.
authors.forename: Ilenia
authors.initials: I
authors.lastname: Fuoco
authors.affiliation: Azienda Ospedaliera Universitaria Pisana, Unità Operativa di Gastroenterologia, Pisa, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: di Fluri
authors.affiliation: Azienda Ospedaliera Universitaria Pisana, Unità Operativa di Gastroenterologia, Pisa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Costa
authors.affiliation: Azienda Ospedaliera Universitaria Pisana, Unità Operativa di Gastroenterologia, Pisa, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Ricchiuti
authors.affiliation: Azienda USL 5, Unità Operativa Chirurgia, Ospedale F. Lotti, Pontedera, Italy.
authors.forename: Graziano
authors.initials: G
authors.lastname: Biondi
authors.affiliation: Azienda Ospedaliera Universitaria Pisana, Unità Operativa di Anatomia e Istologia Patologica 2, Pisa, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Nardini
authors.affiliation: Unità di Genetica, Dipartimento di Biologia, University of Pisa, Pisa, Italy.|Research Center Nutraceuticals and Food for Health-Nutrafood, University of Pisa, Pisa, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Scarpato
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D001706:Biopsy; D002478:Cells, Cultured; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003111:Colonic Polyps / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004249:DNA Damage; D005260:Female; D042822:Genomic Instability; D005982:Glutathione Transferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D012007:Rectum / Q000378:metabolism / Q000473:pathology
chemical_list: C468783:H2AX protein, human; D006657:Histones; C490476:GSTO1 protein, human; D005982:Glutathione Transferase
keywords: GSTO1; Gerotarget; colorectal cancer; genomic instability; micronuclei; γH2AX