PMID- 12714697
OWN - NLM
STAT- MEDLINE
DCOM- 20040123
LR  - 20190513
IS  - 0267-8357 (Print)
IS  - 0267-8357 (Linking)
VI  - 18
IP  - 3
DP  - 2003 May
TI  - Aneugenic potential of okadaic acid revealed by the micronucleus assay combined 
      with the FISH technique in CHO-K1 cells.
PG  - 293-8
AB  - Okadaic acid (OA) is a major toxin involved in diarrhetic shellfish poisoning in 
      humans and has been shown to be both a potent tumor promoter in rodent skin and 
      stomach and an inhibitor of serine/threonine protein phosphatases, specifically 
      PP1 and PP2A. The research on the genotoxic potential of OA amounts to only a few 
      studies, which give conflicting results. In order to evaluate the ability of OA 
      to induce DNA damage, the cytokinesis-block micronucleus assay was performed in 
      the CHO-K1 cell line. A statistically significant induction of micronuclei 
      without strong cytotoxicity was obtained after a 24 h treatment with 20 
      (approximately 5-fold) and 30 nM (approximately 10-fold) OA. Then, in order to 
      discriminate between a clastogenic or aneugenic effect of OA, the micronucleus 
      assay was carried out in combination with fluorescence in situ hybridization 
      (FISH) using a (TTAGGG)(n) DNA probe for centromere detection. FISH analysis 
      showed that OA mainly induced centromere-positive micronuclei (68.9% induction 
      with 20 nM OA and 77.0% with 30 nM). Therefore, OA can be considered aneugenic. 
      Using the same assay, biotransformation of OA was studied after a 4 h treatment 
      with and without metabolic activation. The results show that reactive metabolites 
      of OA were generated with a significant increase in genotoxic potential. The 
      relationship between the different components involved in the mitotic process and 
      OA inhibition of protein phosphatase is also discussed.
FAU - Le Hegarat, Ludovic
AU  - Le Hegarat L
AD  - AFSSA, Laboratoire d'Etudes et de Recherches sur les Medicaments Veterinaires et 
      les Desinfectants, Unite de Toxicologie Alimentaire, BP 90203, F-35302 Fougeres, 
      France.
FAU - Puech, Lilian
AU  - Puech L
FAU - Fessard, Valerie
AU  - Fessard V
FAU - Poul, Jean Michel
AU  - Poul JM
FAU - Dragacci, Sylviane
AU  - Dragacci S
LA  - eng
PT  - Journal Article
PL  - England
TA  - Mutagenesis
JT  - Mutagenesis
JID - 8707812
RN  - 0 (Aneugens)
RN  - 1W21G5Q4N2 (Okadaic Acid)
SB  - IM
MH  - Aneugens/*pharmacology
MH  - Animals
MH  - CHO Cells
MH  - Cricetinae
MH  - *Genetic Techniques
MH  - In Situ Hybridization, Fluorescence
MH  - Micronuclei, Chromosome-Defective/*metabolism
MH  - Micronucleus Tests
MH  - Okadaic Acid/*pharmacology
EDAT- 2003/04/26 05:00
MHDA- 2004/01/24 05:00
CRDT- 2003/04/26 05:00
PHST- 2003/04/26 05:00 [pubmed]
PHST- 2004/01/24 05:00 [medline]
PHST- 2003/04/26 05:00 [entrez]
AID - 10.1093/mutage/18.3.293 [doi]
PST - ppublish
SO  - Mutagenesis. 2003 May;18(3):293-8. doi: 10.1093/mutage/18.3.293.