8-Oxoguanine

Last updated
8-Oxoguanine [1]
8-Oxoguanine.png
Names
IUPAC name
2-Amino-7,9-dihydro-1H-purine-6,8-dione
Other names
7,8-Dihydro-8-oxoguanine; 8-Oxo-7,8-dihydroguanine
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.024.578 OOjs UI icon edit-ltr-progressive.svg
MeSH 8-hydroxyguanine
PubChem CID
UNII
  • InChI=1S/C5H3N5O2/c6-4-8-2-1(3(11)10-4)7-5(12)9-2/h(H3,6,8,9,10,11,12) Yes check.svgY
    Key: UBKVUFQGVWHZIR-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C5H5N5O2/c6-4-8-2-1(3(11)10-4)7-5(12)9-2/h(H5,6,7,8,9,10,11,12)
    Key: CLGFIVUFZRGQRP-UHFFFAOYAZ
  • InChI=1/C5H3N5O2/c6-4-8-2-1(3(11)10-4)7-5(12)9-2/h(H3,6,8,9,10,11,12)
    Key: UBKVUFQGVWHZIR-UHFFFAOYAW
  • O=C2NC=1N\C(=N/C(=O)C=1N2)N
  • c12=NC(=O)N=c1[nH]c(nc2=O)N
Properties
C5H5N5O2
Molar mass 167.128 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

8-Oxoguanine (8-hydroxyguanine, 8-oxo-Gua, or OH8Gua) is one of the most common DNA lesions resulting from reactive oxygen species [2] modifying guanine, and can result in a mismatched pairing with adenine resulting in G to T and C to A substitutions in the genome. [3] In humans, it is primarily repaired by DNA glycosylase OGG1. It can be caused by ionizing radiation, in connection with oxidative metabolism.

Contents

8-oxoG (syn) in a Hoogsteen base pair with dA (anti) 8-oxoG forming Hoogsten base pair with dA.svg
8-oxoG (syn) in a Hoogsteen base pair with dA (anti)
For comparison here is a standard (non-mutagenic) GC base pair with both bases in the anti configuration of the bond between base and sugar. GC base pair jypx3.png
For comparison here is a standard (non-mutagenic) GC base pair with both bases in the anti configuration of the bond between base and sugar.

In body fluids

Increased concentrations of 8-oxoguanine in body fluids have been found to be associated with increased risk of mutagenesis and carcinogenesis. [4] [5]

Care must be taken in the assay of 8-oxoguanine due to the ease with which it can be oxidised during extraction and the assay procedure. [6]

Cancer, aging, infertility

The role of the deoxyriboside form of 8-oxoguanine, 8-oxo-2'-deoxyguanosine (abbreviated 8-oxo-dG or 8-OHdG) in cancer and aging also applies to 8-oxoguanine. Oxoguanine glycosylase is employed in the removal of 8-oxoguanine from DNA by the process of base excision repair. As described in oxoguanine glycosylase, deficient expression of this enzyme causes 8-oxoguanine to accumulate in DNA. This accumulation may then lead upon replication of DNA to mutations including some that contribute to carcinogenesis. 8-oxoguanine is usually formed by the interaction of reactive oxygen species (ROS) with the guanine base in DNA under conditions of oxidative stress; as noted in the article about them, such species may have a role in aging and male infertility, and 8-oxoguanine can be used to measure such stress.

References

  1. ↑ 8-hydroxyguanine - Compound Summary, PubChem
  2. ↑ Kanvah, S.; et al. (2010). "Oxidation of DNA: Damage to Nucleobases". Acc. Chem. Res. 43 (2): 280–287. doi:10.1021/ar900175a. PMID   19938827.
  3. ↑ Cheng KC; Cahill DS; Kasai H; Nishimura S; Loeb LA (Jan 5, 1992). "8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G→T and C→A substitutions". J Biol Chem. 267 (1): 166–72. doi: 10.1016/S0021-9258(18)48474-8 . PMID   1730583.
  4. ↑ Kasai, H (December 1997). "Analysis of a form of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis". Mutation Research. 387 (3): 147–63. doi:10.1016/s1383-5742(97)00035-5. PMID   9439711.
  5. ↑ Halliwell, B (December 1998). "Can oxidative DNA damage be used as a biomarker of cancer risk in humans? Problems, resolutions and preliminary results from nutritional supplementation studies". Free Radical Research. 29 (6): 469–86. doi:10.1080/10715769800300531. PMID   10098453.
  6. ↑ Ravanat, JL; Douki, T; Duez, P; Gremaud, E; Herbert, K; Hofer, T; Lasserre, L; Saint-Pierre, C; Favier, A; Cadet, J (November 2002). "Cellular background level of 8-oxo-7,8-dihydro-2'-deoxyguanosine: an isotope based method to evaluate artefactual oxidation of DNA during its extraction and subsequent work-up". Carcinogenesis. 23 (11): 1911–8. doi: 10.1093/carcin/23.11.1911 . PMID   12419840.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.