Chemistry:Thymine glycol

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Thymine glycol
Thymine glycol.svg
Names
IUPAC name
5,6-Dihydroxy-5-methyldihydro-2,4(1H,3H)-pyrimidinedione
Other names
5,6-Dihydroxy-5,6-dihydrothymine
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
Properties
C5H8N2O4
Molar mass 160.129 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references
Tracking categories (test):

Thymine glycol (5,6-dihydroxy-5,6-dihydrothymine) is one of the principal DNA lesions that can be induced by oxidation and ionizing radiation.[1]

Aging, stroke

The rate at which oxidative reactions generate thymine glycol and thymidine glycol in the DNA of humans is estimated to be about 300 per cell per day.[2] Oxidized DNA bases that are excised by DNA repair processes are excreted in urine. On a body weight basis, mice excrete 18 times more thymine glycol plus thymidine glycol than humans, and monkeys four times more than humans.[2] It was proposed that rate of occurrence of oxidative DNA damages correlates with metabolic rate, and that a higher rate of oxidative damage might cause a higher rate of cellular aging.[2]

Base excision repair is a major DNA repair pathway for removal of oxidative DNA damages. The rate of repair of thymine glycol damage in human fibroblasts was found to decrease with age.[3] Brain samples from humans who died of stroke were found to be deficient in base excision repair of thymine glycol as well as other types of oxidative damages.[4] It was suggested that impaired base excision repair is a risk factor for ischemic brain injury.[4]


References

  1. Basu, AK; Loechler, EL; Leadon, SA; Essigmann, JM (1989). "Genetic effects of thymine glycol: site-specific mutagenesis and molecular modeling studies.". Proc. Natl. Acad. Sci. U.S.A. 86 (20): 7677–81. doi:10.1073/pnas.86.20.7677. PMID 2682618. Bibcode1989PNAS...86.7677B. 
  2. 2.0 2.1 2.2 "Oxidative damage to DNA: relation to species metabolic rate and life span". Proc. Natl. Acad. Sci. U.S.A. 85 (8): 2706–8. 1988. doi:10.1073/pnas.85.8.2706. PMID 3128794. Bibcode1988PNAS...85.2706A. 
  3. "Age-associated modifications of Base Excision Repair activities in human skin fibroblast extracts". Mech. Ageing Dev. 131 (11–12): 661–5. 2010. doi:10.1016/j.mad.2010.09.002. PMID 20854835. 
  4. 4.0 4.1 "Partial loss of the DNA repair scaffolding protein, Xrcc1, results in increased brain damage and reduced recovery from ischemic stroke in mice". Neurobiol. Aging 36 (7): 2319–30. 2015. doi:10.1016/j.neurobiolaging.2015.04.004. PMID 25971543.