Formation of S-[1-(N2-Deoxyguanosinyl)methyl]glutathione between Glutathione and DNA Induced by Formaldehyde
- 18 February 2009
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 131 (10), 3414-3415
- https://doi.org/10.1021/ja808048c
Abstract
Formaldehyde is an essential metabolic intermediate in human cells and can also enter into the body through environmental exposures. It is classified as a human and animal carcinogen according to the International Agency for Research on Cancer (IARC). Previous research has demonstrated that formaldehyde is genotoxic, causing mutations in multiple genes. However, no exogenous formaldehyde-induced DNA adducts have been detected in animals after inhalation exposure, although formaldehyde can result in N6-deoxyadenosine, N2-deoxyguanosine, and N4-deoxycytidine adducts in vitro. This can be partially attributed to the rapid metabolism of formaldehyde by glutathione (GSH)-dependent enzyme systems. Among the intermediates in the pathway of formaldehyde detoxication, S-hydroxymethylglutathione is a reactive species and has the potential to further conjugate with DNA bases. Here, we have demonstrated the formation of S-[1-(N2-deoxyguanosinyl)methyl]glutathione between glutathione and DNA in the presence of formaldehyde. This adduct is unique because of the involvement of S-hydroxymethylglutathione which is a key player during the detoxication of formaldehyde.Keywords
This publication has 19 references indexed in Scilit:
- Formaldehyde-Induced Histone Modifications in VitroChemical Research in Toxicology, 2008
- Glutathione traps formaldehyde by formation of a bicyclo[4.4.1]undecane adductOrganic & Biomolecular Chemistry, 2007
- Loss of DNA–protein crosslinks from formaldehyde-exposed cells occurs through spontaneous hydrolysis and an active repair process linked to proteosome functionCarcinogenesis: Integrative Cancer Research, 2000
- DNA interstrand cross-linking by formaldehyde: nucleotide sequence preference and covalent structure of the predominant cross-link formed in synthetic oligonucleotidesJournal of the American Chemical Society, 1993
- Formaldehyde preferentially interstrand cross-links duplex DNA through deoxyadenosine residues at the sequence 5'-d(AT)Journal of the American Chemical Society, 1992
- Isotope effects and their implications for the covalent binding of inhaled [3H]- and [14C]formaldehyde in the rat nasal mucosaToxicology and Applied Pharmacology, 1987
- Further studies of the metabolic incorporation and covalent binding of inhaled [3H]- and [14C]formaldehyde in Fischer-344 rats: Effects of glutathione depletionToxicology and Applied Pharmacology, 1987
- Contribution of formaldehyde to respiratory cancer.Environmental Health Perspectives, 1986
- Determination of formaldehyde in biological tissues by gas chromatography/mass spectrometryJournal of Mass Spectrometry, 1982
- Formaldehyde as a probe of DNA structure. I. Reaction with exocyclic amino groups of DNA basesBiochemistry, 1975