Sequence-specific alkali-labile lesions in DNA caused by D-isoglucosamine.
The site-specific induction of DNA damage by 1-amino-1-deoxy-D-fructose (D-isoglucosamine) was investigated. When 32P-end-labeled DNA restriction fragments of known sequence were reacted with D-isoglucosamine in the presence of Cu2+, and the DNA products were analyzed on high-resolution denaturing polyacrylamide gels after treatment with aqueous piperidine (1 M) at 90 degrees C for 30 min, the DNA strands were cleaved at pyrimidine residues at a statistically significant frequency, and 80.5% of the extensively damaged sites were induced at pyrimidine residues in dinucleotide sequences of pyrimidine-purine (5'----3'). These cleavages were scarcely observed without piperidine/heat treatment. The damaged DNA sites increased in proportion to the reaction time and concentration of D-isoglucosamine. Metal-chelating agents (EDTA, diethylenetriaminepentaacetic acid) and some oxygen radical scavengers inhibited the induction of alkali-labile lesions. These results indicate that some oxygen radicals are involved in the induction of alkali-labile lesions.
D001483:Base Sequence; D002614:Chelating Agents / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA; D005609:Free Radicals; D019270:Fructosamine; D006595:Hexosamines; D010100:Oxygen / Q000633:toxicity
D002614:Chelating Agents; D005609:Free Radicals; D006595:Hexosamines; D019270:Fructosamine; D004247:DNA; D010100:Oxygen