Cellular replicative clock

Cell tines offer several advantages over primary cell cultures, such as an unlimited life-span and the lack of time-consuming isolation procedures. Additionally once established, they are often more stable than primary cells which are usually in a continuous state of de-differentiation. Thus, the majority of in vitro nephrotoxicity studies have been performed on renal epithelial cell tines. In normal somatic cells, telomeres, the tandemly repeated hexamers at the end of mammalian chromosomes, act as the cellular replicative clock [43] and shorten at each cell division. Once telomeres have exceeded a certain critical length, the so called "Hayflick limit" [44], the cell enters replicative senescence and no longer proliferates. Until recently the most widely used renal cell tines were those which arose from spontaneously acquired immortalization in culture. These cell tines include LLC-PK (Hampshire pig) [45,46], JTC-12 (cynomolgus monkey) [47] and OK (American opossum) [48] cells, which exhibit biochemical and antigenic characteristics suggestive of proximal... 

Eukaryotic DNA is equipped with special ends called telomers. Telomers are made up of hexanucleotide sequences that repeat at the ends of the DNA. For example, human DNA features repeating AGGGTT sequences. Functionally, telomers protect the ends of chromosomes from being treated as a broken piece of DNA in need of repair. Interestingly, telomers are cut off each time the DNA is replicated, indicating a possible cellular clock that allows only a certain number of cellular replications. Telomerase is the enzyme that catalyzes the synthesis of telomers. Telomerase is present in limited quantities within certain cells such as fetal tissue, adult male germ cells, and stem cells. It is also found in over 85% of tumor cells. Researchers speculate that the telomerase activity may be linked to cancer. Propose an explanation for why telomerase activity could be associated with cancer and speculate on ways in which cancer treatments in the future may capitalize on research on this enzyme. 

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