DNA strand breaks induced through active oxygen radicals by fragrant component 4-hydroxy-2-hydroxymethyl-5-methyl-3(2H)-furanone in Maillard reaction of hexose/amino acid.
The Maillard reaction of glucose/amino acid produces components that induce strand breakage of supercoiled DNA. This study was designed to elucidate the structure of the active components and the mechanisms of their DNA strand breakage. When an aqueous mixture of glucose/glycine heated under reflux for 4 hr was extracted with ethyl acetate, the extract showed mutagenicity to Salmonella typhimurium TA100 and strand-breaking activity for supercoiled DNA. One of the components with DNA strand-breaking activity was isolated by repeated HPLC using a reverse phase column. The component was identified as 4-hydroxy-2-hydroxymethyl-5-methyl-3(2H)-furanone (HHMF), a fragrant component in the Maillard reaction mixture. HHMF was similarly produced in the reaction of glucose/alanine and fructose/glycine. DNA strand-breaking activity of the component at pH 7.4 increased with increasing dose of the component and with increasing incubation time. The strand-breaking activity of the component was greater at pH 7.4 than at pH 4.4 and 9.4; it was inhibited in the presence of superoxide dismutase, catalase, hydroxyl radical scavengers, spin-trapping agents, thiol compounds and metal chelators, and also by removal of dissolved oxygen from the reaction mixture. The strand-breaking activity was enhanced in the presence of ionic iron. Incubation of HHMF with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) gave electron spin resonance signals characteristics of the DMPO-OH adduct, indicating generation of the hydroxyl radical. HHMF generated superoxide, hydrogen peroxide and then hydroxyl radical with the aid of a trace amount of metal ions, which effectively cleaved the DNA strand.
Hiramoto
K
K
Tokyo College of Pharmacy, Japan.
Sekiguchi
K
K
Aso-O
R
R
Ayuha
K
K
Ni-Iyama
H
H
Kato
T
T
Kikugawa
K
K
D000596:Amino Acids; D004249:DNA Damage / Q000187:drug effects; D004269:DNA, Bacterial / Q000187:drug effects*; D005609:Free Radicals / Q000494:pharmacology; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006601:Hexoses; D006863:Hydrogen-Ion Concentration; D015416:Maillard Reaction; D008970:Molecular Weight; D009152:Mutagenicity Tests; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics
D000596:Amino Acids; D004269:DNA, Bacterial; D005609:Free Radicals; D005663:Furans; D006601:Hexoses; C085025:5-hydroxymethyl-3(2H)-furanone