Marine toxin domoic acid induces in vitro genomic alterations in human peripheral blood cells

Domoic acid (DA) is an excitatory marine neurotoxin produced by diatoms Pseudo-nitzschia spp. as a defence compound that accumulates in the food web and is associated with amnesic shellfish poisoning in humans. Although its toxicity has been well established in marine species, there is limited data on DA cytogenotoxicity in human non-target cells. Therefore, we aimed to investigate the cytogenotoxic potential of DA (0.01-10 μg/mL) in human peripheral blood cells (HPBCs) using a battery of bioassays in vitro. In addition, the influence of DA on oxidative stress parameters as a possible mechanism of action was assessed. Results revealed that DA induced dose- and time-dependent cytotoxic effects. DA significantly affected genomic instability by increasing the frequency of micronuclei and nuclear buds. Furthermore, a slight induction of primary DNA strand breaks was detected after 24 h of exposure accompanied by a significant increase in the number of abnormal size tailed nuclei. No induction of hOGG1 (human 8-oxoguanine DNA glycosylase) sensitive sites was determined upon exposure to DA. Additionally, DA induced oxidative stress by increased production of reactive oxygen species accompanied by changes in glutathione, superoxide dismutase, malondialdehyde and protein carbonyl levels. Overall, the obtained results showed adverse genotoxic effects of DA in non-target HPBCs.