Free radical-scavenging activity and DNA damaging potential of auxins IAA and 2-methyl-IAA evaluated in human neutrophils by the alkaline comet assay.
Auxins, of which indole-3-acetic acid (IAA) is the most widespread representative, are plant hormones. In addition to plants, IAA also naturally occurs in humans in micromolar concentrations. In the presence of peroxidase, indolic auxins are converted to cytotoxic oxidation products and have thus been proposed for use in gene-directed enzyme/prodrug tumor therapy. Since data on the genotoxicity of IAA and its derivatives are not consistent, here we investigate the early DNA damaging effects (2-h treatment) of the auxins, IAA, and 2-methyl-indole-3-acetic acid (2-Me-IAA) by the alkaline comet assay and compare them with their free radical-scavenging activity measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Human neutrophils are chosen as the test system since they possess inherent peroxidase activity. The results of the comet assay indicate an increase in DNA damage in a dose-dependent manner up to 1.00 mM of both auxins. Generally, IAA applied in the same concentration had greater potential to damage DNA in human neutrophils than did 2-Me-IAA. The genotoxicities of the two examined auxins are negatively correlated with their antioxidant activities, as measured by the DPPH assay; 2-Me-IAA showed a higher antioxidant capacity than did IAA. We assume that differences in the molecular structure of the tested auxins contributed to differences in their metabolism, in particular, with respect to interactions with peroxidases and other oxidative enzymes in neutrophils. However, the exact mechanisms have to be elucidated in future studies.
Salopek-Sondi
Branka
B
Ruder Bosković Institute, Bijenicka 54, HR-10 000 Zagreb, Croatia.
Piljac-Zegarac
Jasenka
J
Magnus
Volker
V
Kopjar
Nevenka
N
D000328:Adult; D020552:Comet Assay / Q000379:methods*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D007210:Indoleacetic Acids / Q000494:pharmacology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism
C552594:2-methyl-indole-3-acetic acid; D016166:Free Radical Scavengers; D007210:Indoleacetic Acids; C030737:indoleacetic acid