Abstract
Okadaic Acid (OA) the major diarrheic shellfish poisoning (DSP) toxin is known as a tumor promoter and seems likely implicated in the genesis of digestive cancer. Little is known regarding genotoxicity and carcinogenicity of Domoic Acid (DA), the major Amnesic Shellfish Poisoning (ASP) toxin. Both OA and DA occur in seafood and are of human health concerns. Micronuclei (MN) arise from abnormalities in nuclear division during mitosis due to a failure of the mitotic spindle or by complex chromosomal configurations that pose problems during anaphase. In order to evaluate the ability of okadaic acid (OA) and domoic acid (DA) to induce DNA damage we performed the micronucleus assay using the Caco-2 cell line. To discriminate between a clastogenic or aneugenic effect of OA and DA, the micronucleus assay was conducted by cytokinesis-block micronucleus assay using cytochalasin B with Giemsa staining and/or acridine orange staining, in parallel to fluorescence in situ hybridization (FISH) using a concentrated human pan-centromeric chromosome paint probe. Our results showed that OA and DA significantly increased the frequency of MN in Caco-2 cells. The MN caused by OA are found in mononucleated cells and binucleated cells, whereas those caused by DA are mainly in binucleated cells. The results of FISH analysis showed that OA induced centromere-positive micronuclei and DA increased the percentage of MN without a centromeric signal. In conclusion, both OA and DA bear mutagenic potential as revealed in Caco-2 cells by induction of MN formation. Moreover, OA induced whole chromosome loss suggesting a specific aneugenic potential, whereas DA seems simply clastogenic. At present, one cannot rule out possible DNA damage of intestinal cells if concentrations studied are reached in vivo, since this may happen with concentrations of toxins just below regulatory limits in case of frequent consumption of contaminated shell fishes.
Highlights
Among marine phytoplankton about 40 species have the capacity of producing potent toxins [1]
In the present study we confirmed the cytotoxicity of okadaic acid (OA) [9] and we showed that Domoic acid (DA) is cytotoxic to the human intestinal cell line Caco-2
Using the respective cytotoxic concentrations we have evaluated the ability of these toxins to produce nuclear abnormalities in term of micronuclei (MN)
Summary
Among marine phytoplankton about 40 species have the capacity of producing potent toxins [1] Among these toxins, okadaic acid (OA) and domoic acid (DA) are considered important since they accumulate in filterfeeding animals consumed by humans, representing an environmental and public health problem [2, 3]. Okadaic acid (OA) and domoic acid (DA) are considered important since they accumulate in filterfeeding animals consumed by humans, representing an environmental and public health problem [2, 3] Both could be ingested either separately or in combination with different types of sea foods. Intestinal cells seem to be suitable to use to study both phycotoxins in vitro. Caco-2 cells from that point of view have been intensively used to study several toxicants that are normally ingested for their transport, biotransformation and mode of action in vitro [9,10,11]
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