I found an interesting paper describing the formation of DNA adducts in quiescent cells arrested for DNA synthesis and the necessity for the cell to enter the cell proliferation stage for DNA synthesis to occur, resulting in the repair of DNA adducts (O'Neill, 2000). However, it is also during this DNA synthesis stage that the DNA adducts are processed into cellular mutations. Thus, cell proliferation results in both repair of potentially mutagenic adducts and the processing of mutations in the remainder of the DNA adducts (Bielas and Heddle, 2000).
It is known that adult stem cells can be quiescent for a number of years. Thus, there lies the possibility that the adult stem cells could be exposed to mutagens or electrophilic agents capable of forming adducts with DNA. A portion of them can be processed into mutations when the adult stem cells start proliferating. It has also been found that oxidative stress can induce hematopoietic stem cells to proliferate (Liu and Finkel, 2006, Ito et al, 2006). The question that remains is when the adult stem cell is exposed to mutagen and stresses to the cell from reactive oxygen species, are we witnessing its transformation?
Citations
1) J. Patrick O'Neill. DNA damage, DNA repair, cell proliferation, and DNA replication: How do gene mutations result? Proc Natl Acad Sci U S A. 2000 October 10; 97(21): 11137–11139.
2) Bielas JH, Heddle JA. Proliferation is necessary for both repair and mutation in transgenic mouse cells. Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11391-6.
4) Ito K, Hirao A, Arai F, Takubo K, Matsuoka S, Miyamoto K, Ohmura M, Naka K, Hosokawa K, Ikeda Y, Suda T. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med. 2006 Apr;12(4):446-51.
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