Comparative Study of Domoic Acid and Okadaic Acid Induced-chromosomal Abnormalities in the Caco-2 Cell Line

Overview

Journal Int J Environ Res Public Health

Publisher MDPI

Specialties Environmental Health
Public Health

Date 2006 Jul 11

PMID 16823071

Citations 9

Authors

Pinto-Silva Carvalho

R Catian

Serge Moukha

William G Matias

Edmond E Creppy

Affiliations

Soon will be listed here.

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.

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References

Schuler M, Rupa D, Eastmond D . A critical evaluation of centromeric labeling to distinguish micronuclei induced by chromosomal loss and breakage in vitro. Mutat Res. 1997; 392(1-2):81-95. DOI: 10.1016/s0165-1218(97)00047-5. View

Matias W, Traore A, Creppy E . Variations in the distribution of okadaic acid in organs and biological fluids of mice related to diarrhoeic syndrome. Hum Exp Toxicol. 1999; 18(5):345-50. DOI: 10.1191/096032799678840156. View

Ouanes Z, Ayed-Boussema I, Baati T, Creppy E, Bacha H . Zearalenone induces chromosome aberrations in mouse bone marrow: preventive effect of 17beta-estradiol, progesterone and Vitamin E. Mutat Res. 2005; 565(2):139-49. DOI: 10.1016/j.mrgentox.2004.10.005. View

Johnson D, Yamaji S, Tennant J, Srai S, Sharp P . Regulation of divalent metal transporter expression in human intestinal epithelial cells following exposure to non-haem iron. FEBS Lett. 2005; 579(9):1923-9. DOI: 10.1016/j.febslet.2005.02.035. View

Nesti C, Trippi F, Scarpato R, Migliore L, Turchi G . Cytokinesis-block micronucleus assay in primary human liver fibroblasts exposed to griseofulvin and mitomycin C. Mutagenesis. 2000; 15(2):143-7. DOI: 10.1093/mutage/15.2.143. View

Traore A, Ruiz S, Baudrimont I, Sanni A, Dano S, Guarigues P . Combined effects of okadaic acid and cadmium on lipid peroxidation and DNA bases modifications (m5dC and 8-(OH)-dG) in Caco-2 cells. Arch Toxicol. 2000; 74(2):79-84. DOI: 10.1007/s002040050656. View

Cordier S, Monfort C, Miossec L, Richardson S, Belin C . Ecological analysis of digestive cancer mortality related to contamination by diarrhetic shellfish poisoning toxins along the coasts of France. Environ Res. 2000; 84(2):145-50. DOI: 10.1006/enrs.2000.4103. View

Rossini G, Sgarbi N, Malaguti C . The toxic responses induced by okadaic acid involve processing of multiple caspase isoforms. Toxicon. 2001; 39(6):763-70. DOI: 10.1016/s0041-0101(00)00202-6. View

Traore A, Baudrimont I, Ambaliou S, Dano S, Creppy E . DNA breaks and cell cycle arrest induced by okadaic acid in Caco-2 cells, a human colonic epithelial cell line. Arch Toxicol. 2001; 75(2):110-7. DOI: 10.1007/s002040000188. View

10.

Dizer H, Fischer B, Harabawy A, Hennion M, Hansen P . Toxicity of domoic acid in the marine mussel Mytilus edulis. Aquat Toxicol. 2001; 55(3-4):149-56. DOI: 10.1016/s0166-445x(01)00178-3. View

11.

Chung H, Kang S, Kim S . A combination of the micronucleus assay and a FISH technique for evaluation of the genotoxicity of 1,2,4-benzenetriol. Mutat Res. 2002; 516(1-2):49-56. DOI: 10.1016/s1383-5718(02)00018-9. View

12.

Pinto-Silva C, Ferreira J, Costa R, Filho P, Creppy E, Matias W . Micronucleus induction in mussels exposed to okadaic acid. Toxicon. 2002; 41(1):93-7. DOI: 10.1016/s0041-0101(02)00214-3. View

13.

Creppy E, Traore A, Baudrimont I, Cascante M . Recent advances in the study of epigenetic effects induced by the phycotoxin okadaic acid. Toxicology. 2002; 181-182:433-9. DOI: 10.1016/s0300-483x(02)00489-4. View

14.

Berger V, Gabriel A, Sergent T, Trouet A, Larondelle Y, Schneider Y . Interaction of ochratoxin A with human intestinal Caco-2 cells: possible implication of a multidrug resistance-associated protein (MRP2). Toxicol Lett. 2003; 140-141:465-76. DOI: 10.1016/s0378-4274(03)00043-2. View

15.

Hegarat L, Puech L, Fessard V, Poul J, Dragacci S . Aneugenic potential of okadaic acid revealed by the micronucleus assay combined with the FISH technique in CHO-K1 cells. Mutagenesis. 2003; 18(3):293-8. DOI: 10.1093/mutage/18.3.293. View

16.

Ouanes Z, Abid S, Ayed I, Anane R, Mobio T, Creppy E . Induction of micronuclei by Zearalenone in Vero monkey kidney cells and in bone marrow cells of mice: protective effect of Vitamin E. Mutat Res. 2003; 538(1-2):63-70. DOI: 10.1016/s1383-5718(03)00093-7. View

17.

Traore A, Baudrimont I, Dano S, Sanni A, Larondelle Y, Schneider Y . Epigenetic properties of the diarrhetic marine toxin okadaic acid: inhibition of the gap junctional intercellular communication in a human intestine epithelial cell line. Arch Toxicol. 2003; 77(11):657-62. DOI: 10.1007/s00204-003-0460-0. View

18.

Fujita M, Goto K, Yoshida K, Okamura H, Morimoto H, Kito S . Okadaic acid stimulates expression of Fas receptor and Fas ligand by activation of nuclear factor kappa-B in human oral squamous carcinoma cells. Oral Oncol. 2003; 40(2):199-206. DOI: 10.1016/s1368-8375(03)00152-0. View

19.

Jeffery B, Barlow T, Moizer K, Paul S, Boyle C . Amnesic shellfish poison. Food Chem Toxicol. 2004; 42(4):545-57. DOI: 10.1016/j.fct.2003.11.010. View

20.

Hegarat L, Fessard V, Poul J, Dragacci S, Sanders P . Marine toxin okadaic acid induces aneuploidy in CHO-K1 cells in presence of rat liver postmitochondrial fraction, revealed by cytokinesis-block micronucleus assay coupled to FISH. Environ Toxicol. 2004; 19(2):123-8. DOI: 10.1002/tox.20004. View