PMID- 16823071 OWN - NLM STAT- MEDLINE DCOM- 20070130 LR - 20191110 IS - 1661-7827 (Print) IS - 1660-4601 (Electronic) IS - 1660-4601 (Linking) VI - 3 IP - 1 DP - 2006 Mar TI - Comparative study of Domoic Acid and Okadaic Acid induced-chromosomal abnormalities in the Caco-2 cell line. PG - 4-10 AB - 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. FAU - Carvalho, Pinto-Silva AU - Carvalho PS AD - Department of Environmental Engineering, Toxicological Laboratory of the Federal University of Santa Catarina, Brazil Campus Universitario, Trindade 88040-900, Brazil. FAU - Catian, R AU - Catian R FAU - Moukha, Serge AU - Moukha S FAU - Matias, William G AU - Matias WG FAU - Creppy, Edmond E AU - Creppy EE LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Switzerland TA - Int J Environ Res Public Health JT - International journal of environmental research and public health JID - 101238455 RN - 0 (Mutagens) RN - 1W21G5Q4N2 (Okadaic Acid) RN - M02525818H (domoic acid) RN - SIV03811UC (Kainic Acid) SB - IM MH - Caco-2 Cells MH - *Chromosome Aberrations MH - Dose-Response Relationship, Drug MH - Humans MH - In Situ Hybridization, Fluorescence MH - Kainic Acid/*analogs & derivatives/toxicity MH - Micronucleus Tests MH - Mutagens/*toxicity MH - Okadaic Acid/*toxicity PMC - PMC3785674 EDAT- 2006/07/11 09:00 MHDA- 2007/01/31 09:00 PMCR- 2006/03/01 CRDT- 2006/07/11 09:00 PHST- 2006/07/11 09:00 [pubmed] PHST- 2007/01/31 09:00 [medline] PHST- 2006/07/11 09:00 [entrez] PHST- 2006/03/01 00:00 [pmc-release] AID - ijerph-03-00004 [pii] AID - 10.3390/ijerph2006030001 [doi] PST - ppublish SO - Int J Environ Res Public Health. 2006 Mar;3(1):4-10. doi: 10.3390/ijerph2006030001.