Chromosome Instability in Patients with Chronic Renal Failure Theodoros Lialiaris, 1 Polyxeni Mavromatidou, 1 Evangelos Digkas, 1 Theoktisti Passadaki, 1 Panagiotis Mpountoukas, 1 Stylianos Panagoutsos, 2 and Vassilios Vargemezis 2 Objective: The aim of this study was to investigate the frequency of sister chromatid exchanges (SCEs), the presence of cytostaticity, cytotoxicity, and therefore, the possible genetic instability in patients with chronic renal failure (CRF) in human cultured peripheral blood lymphocytes. Methods: Peripheral blood lymphocytes were cultured from 32 patients with CRF (average 55.2 years) and 18 healthy blood donors (average 44.6 years), and the SCE method was applied afterward. The increase in SCE frequency was evaluated as an immediate DNA damage index, while the reduction in the values of the proliferating rate indices was evaluated as a cytostatic index and the mitotic indices as a cytotoxic index was also measured. Results: A significant increase in the SCE frequencies along with a significant reduction in mitotic indices was observed in patients with CRF compared with the controls. It is notable that there was no significant difference in SCE levels among patients with CRF and cancer, and patients with CRF alone. Conclusions: This study illustrates increased genetic instability in patients with CRF. These results could also be of a great importance in early diagnosis to prognosticate a possible generation of neoplasm in the future. Introduction C hronic renal failure (CRF) (National Kidney Foun- dation, 2002) is usually the result of a variety of chronic conditions, which include diabetic nephropathy, glomerulo- nephritis, obstructive uropathy, polycystic disease, renal ar- tery stenosis, and tubular dysfunction. Despite more aggressive treatment of diabetes, hypertension, and hyper- lipidemia, the incidence and prevalence rates of end-stage renal disease (ESRD) continue to increase worldwide. The likelihood of developing chronic kidney disease in an indi- vidual is determined by interactions between genes and the environment. A three- to ninefold greater risk of ESRD is observed in individuals with a family history of ESRD (Satko et al., 2005). Genetic factors, environmental factors, and their interac- tions are implicated in the development of ESRD. Also, there are a number of candidate genes, which are responsible for the initiation of renal failure or affecting its progression (Bur- aczynska and Ksiazek, 2001). ESRD patients have an increased risk of carcinoma of the kidney, as a result of de- velopment of a disproportionately high number of papillary renal-cell carcinomas (RCCs) (Chudek et al., 1998; Hughson et al., 1999). RCCs are responsible for the deaths of 3–4% of the patients with ESRD. The clear-cell carcinoma of the kidney shows a deletion of gene sequences in the short arm of chromosome 3 (3p). In contrast to the general population, RCCs with 3p abnormalities represent only a small proportion of the renal carcinomas in ESRD tumors. RCCs that arise in ESRD patients have genetic changes that are similar to those found in spo- radic tumors (Hughson et al., 1996a, 1996b). RCCs display different chromosomal abnormalities ac- cording to their morphology; gains of chromosomes 7 and 17 and loss of Y are commonly observed in papillary le- sions, whereas loss of 3p sequences (3p21.3 region is among the most frequently lost) and multiple losses of specific chromosomes are found in nonpapillary and chromophobe cell carcinomas, respectively. Also occasional gain of chromosome 16 is observed in papillary tumors (Gronwald et al., 1999; Huebner, 2001). Further, the fragile histidine triad gene is localized at the most common fragile site at chromosome 3p14.2. This fragile histidine triad gene and the p53 tumor suppressor gene are targets of different en- vironmental agents (Chudek et al., 1998; Dreijerink et al., 2001). Chromosomal fragility is defined as the phenomenon during which automatic mutations (point, structural or nu- merical) appear or are produced by several natural, chemical, or biological factors in different places of one or more chro- mosomes, of one or more cells, in increased levels as regards the genetic material of normal cells (Sutherland, 1988; Departments of 1 Genetics and 2 Nephrology, Faculty of Medicine, Demokrition University of Thrace, Alexandroupolis, Greece. GENETIC TESTING AND MOLECULAR BIOMARKERS Volume 14, Number 1, 2010 ª Mary Ann Liebert, Inc. Pp. 37–41 DOI: 10.1089=gtmb.2009.0109 37