LC-MS Study on the Formation of Cyclic 1,N^2-Propano Guanine Adduct in the Reactions of DNA with Acetaldehyde in the Presence of Histone (Analytical Biochemistry)

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The formation of cyclic 1,N^2-propano guanine (CPr-Gua) adduct is significantly accelerated by the addition of arginine or histone in the reaction of calf thymus DNA with acetaldehyde (AA) or crotonaldehyde (CA). Histone proteins, containing a large amount of basic amino acids such as arginine, are essential as nucleosome cores to package DNA. In the presence of 0.60% (w/v) histone in the reaction mixture, 8-times and 25-times larger amounts of the CPr-Gua adduct were formed in the reaction of the DNA with AA and CA, respectively, compared with those in the absence of histone. Furthermore, for the DNA incubated at 95 ℃ for 10 min and cooled on ice to make the single-stranded moieties, 72-times and 178-times larger amounts of the CPr-Gua adduct were formed by AA and CA, respectively, in the presence of 0.60% (w/v) histone. These results strongly suggest that DNA in vivo should be exposed to a much more dangerous situation, compared with DNA alone, from the viewpoint of reactivity with the aldehydes. During DNA replication and transcriptional events of cells, the danger will be further increased markedly because of opening of double-strands. Semi-micro HPLC-ESI-MS measurements following deprination of DNA samples were performed for quantification of the adduct as the corresponding base form, CPr-Gua, in evaluation of the reactivity of DNA with AA and CA.
公益社団法人日本薬学会の論文
2004-03-01