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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 are indolic compounds commonly known as plant hormones. Their most common representative, indole-3-acetic acid (IAA), also naturally occurs in humans in micromolar concentrations. By peroxidase, indolic auxins are converted to cytotoxic oxidation products and have thus been proposed for use in gene directed enzyme/prodrug tumor therapy (GDEPT). Since the data on the genotoxicity of IAA and its derivatives are not consistent, here we investigated the early DNA damaging effects (2h treatment) of the auxins, indole-3-acetic acid (IAA) and 2-methyl- indole-3-acetic acid (2-Me-IAA) by the alkaline comet assay and compare them to their free radical scavenging activity measured by the DPPH assay. Human neutrophils are chosen as test system since they possess an inherent peroxidase activity. The results of the comet assay indicate increase in DNA damage in a dose-dependent manner up to 1.00 mM of both auxins. Generally, IAA applied in the same concentrations had greater potential to damage DNA in human neutrophils than 2-Me-IAA. The genotoxicities of the two examined auxins are shown to be negatively correlated with their antioxidant activities, as measured by the DPPH assay ; 2-Me-IAA showed a higher antioxidant capacity in comparison to IAA. We assume that differences in the molecular structure of the tested auxins contributed to the differences in their metabolism, especially interactions with peroxidases and other related enzymes in neutrophils. However, the exact mechanisms have to be elucidated in future studies.

neutrophils; indole acetic acid; 2-methylindole acetic acid; free radical scavenging activity; alkaline comet assay; DNA damage

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