title: DNA modifications by the mutagen glyoxal: adduction to G and C, deamination of C and GC and GA cross-linking.
abstract: The mutagen glyoxal was reacted with DNA or deoxynucleosides under physiological conditions (pH 7.4, 37 degrees C) in vitro and the products were analyzed by HPLC coupled with a photodiode array UV detector. The efficient formation of a cyclic glyoxal-dG adduct (dG+) was observed in DNA, as well as with dG. The monomeric dG + was gradually decomposed to dG at pH 7.4 and 37 degrees C (t1/2 14.8 h). However, the dG+ formed in single- and double-stranded DNA was rather stable under physiological conditions and the half-lives were 19 and 40 times longer respectively than that of the monomer (t1/2 285 and 595 h respectively). By reaction of glyoxal with deoxycytidine (dC), the deamination products deoxyuridine and 5-hydroxyacetyl-dC (dC+) were formed. Under the same conditions, 5-methyl-dC was deaminated to dT at a higher rate. Deoxyuridine was also formed in DNA by glyoxal treatment. When glyoxal was reacted with various combinations of deoxynucleosides for a prolonged period, dG-glyoxal-dC (GgC), dG-glyoxal-dA (GgA), dG-glyoxal-dG (GgG) and dC-glyoxal-dC (CgC) cross-links were detected, although structures were not assigned unequivocally. Among these, the former two, the GC and GA cross-links, were detected in glyoxal-treated DNA. The yields of these products in DNA were in the following order; dG+ > dU > GgA > GgC > dC+. These DNA modifications may be relevant to glyoxal-induced mutations at GC pairs.
authors.affiliation: Department of Environmental Oncology, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kasai
authors.forename: N
authors.initials: N
authors.lastname: Iwamoto-Tanaka
authors.forename: S
authors.initials: S
authors.lastname: Fukada
mesh_terms: D003596:Cytosine / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism*; D003641:Deamination; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000378:metabolism*; D003849:Deoxyguanosine / Q000378:metabolism*; D003857:Deoxyuridine / Q000378:metabolism; D006037:Glyoxal / Q000378:metabolism*; D006147:Guanine / Q000378:metabolism; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism
chemical_list: D018736:DNA Adducts; D003841:Deoxycytidine; D006037:Glyoxal; D006147:Guanine; D003596:Cytosine; C016569:5-methyldeoxycytidine; D015719:Single-Strand Specific DNA and RNA Endonucleases; D003849:Deoxyguanosine; D013936:Thymidine; D003857:Deoxyuridine