Telomeres play a vital role in protecting the ends of chromosomes and preventing chromosome fusion. The failure of cancer cells to properly maintain telomeres can be an important source of the chromosome instability involved in cancer cell progression. Telomere loss results in sister chromatid fusion and prolonged breakage/fusion/bridge (B/F/B) cycles, leading to extensive DNA amplification and large deletions. These B/F/B cycles end primarily when the unstable chromosome acquires a new telomere by translocation of the ends of other chromosomes. Many of these translocations are nonreciprocal, resulting in the loss of the telomere from the donor chromosome, providing a mechanism for transfer of instability from one chromosome to another until a chromosome acquires a telomere by a mechanism other than nonreciprocal translocation. B/F/B cycles can also result in other forms of chromosome rearrangements, including double-minute chromosomes and large duplications. Thus, the loss of a single telomere can result in instability in multiple chromosomes, and generate many of the types of rearrangements commonly associated with human cancer.
"Indeed, there is a higher incidence of certain tumors in telomerase-Knock-Out (KO) mice that harbor p53 mutations  . Sabatier et al. showed that a single telomere loss can lead to multiple telomere dysfunctions , and several studies have shown that telomere dysfunction was responsible for genomic instability leading to cancer  . More recently, two studies have demonstrated the implication of telomere dysfunction in triggering aggressive tumors. "
"One is centromere inactivation through DNA rearrangements or epigenetic switches at one centromere (Lejeune et al. 1973; Avarello et al. 1992; Kramer et al. 1994; Pennaneach and Kolodner 2009; Mackinnon and Campbell 2011; Sato et al. 2012; Song et al. 2013). The other is telomere addition at the broken ends; for instance, by telomerase or break-induced replication (Murnane and Sabatier 2004; Pennaneach and Kolodner 2009). "
"Among the various environmental factors affecting telomere maintenance, chemical exposure has been detected but insufficiently studied. Many studies have shown that the attrition of telomeres leads to genomic instability associated with various age-related disorders including cancers (Murnane and Sabatier, 2004). Certain types of cancer proven to have short telomeres such as non-Hodgkin's lymphoma , leukemia, brain, breast, kidney, and prostate cancer have been linked with pesticide exposure (Bassil et al., 2007). "
[Show abstract][Hide abstract] ABSTRACT: Agricultural workers are often exposed to high levels of pesticides over prolonged periods of time. We attempted to determine whether exposure to multiple pesticides shortens relative telomere length (RTL) and causes nucleoplasmic bridge (NPB) formation via the mechanism of telomere-end fusion in the lymphocytes of agricultural workers. For measuring RTL, we used quantitative fluorescent in situ hybridization, while NPB frequency was measured as part of the cytome assay. Multivariate analysis of variances taking into account confounding factors (age, gender, years of exposure, smoking, and alcohol intake) did not show a decrease, but rather an increase of RTL in agricultural workers compared to control individuals. In the exposed population, NPB frequency was significantly higher compared to controls (6 times, p<0.05). Multiple regression between NPB, RTL, and confounding factors was not significant. Using Spearman correlation, we did not find proof for our initial hypothesis. Our hypothesis that telomere shortening is a mechanism of NPB origin was not proven, indicating that telomere-end fusion is not a mechanism of NPB formation under our experimental conditions for agricultural workers.
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