PMID- 15037998
OWN - NLM
STAT- MEDLINE
DCOM- 20040812
LR  - 20131121
IS  - 1520-4081 (Print)
IS  - 1520-4081 (Linking)
VI  - 19
IP  - 2
DP  - 2004 Apr
TI  - 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.
PG  - 123-8
AB  - Okadaic acid (OA), a major polyether toxin involved in diarrhetic shellfish 
      poisoning (DSP), is a potent tumor promoter in rodent skin and glandular stomach 
      and a specific inhibitor of the serine/threonine protein phosphatases PP1 and 
      PP2A. A previous study, which used the cytokinesis-block micronucleus (CBMN) 
      assay in CHO-K1 cells, showed that OA induced chromosome damage in the presence 
      of a rat liver metabolic activation system (S9). To support OA biotransformation 
      by S9, the same test system was performed, and DNA damage induced by OA was 
      measured with and without metabolic activation as well as in the presence of 
      heat-inactivated S9 fraction. The results showed that only in the presence of 
      active S9 did OA significantly increased the frequency of micronucleated 
      binucleated (MNBN) cells. After a 4-h treatment a 2- to 5-fold increase of MNBN 
      cells was observed at 30 nM and at 50 nM of OA. However, without S9 or in the 
      presence of heat-inactivated S9, OA did not induce any chromosome damage. We 
      concluded that OA can be metabolically activated in vitro into metabolites that 
      are more genotoxic. The CBMN assay coupled with fluorescence in situ 
      hybridization (FISH) using a DNA probe for centromere detection was performed to 
      discriminate between clastogenic (chromosome breakage) and aneugenic (chromosome 
      loss) effects. FISH analysis showed that OA metabolites increased in a 
      dose-dependent manner in centromere positive micronuclei (CEN+): 60% of CEN+ at 
      30 nM and 75% of CEN+ at 50 nM of OA. The uptake of OA into CHO-K1 cells and the 
      biotransformation of the toxin are discussed.
CI  - Copyright 2004 Wiley Periodicals, Inc. Environ Toxicol 19: 123-128, 2004
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, B.P. 90203, 35302 Fougeres 
      cedex, France.
FAU - Fessard, Valerie
AU  - Fessard V
FAU - Poul, Jean Michel
AU  - Poul JM
FAU - Dragacci, Sylviane
AU  - Dragacci S
FAU - Sanders, Pascal
AU  - Sanders P
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Environ Toxicol
JT  - Environmental toxicology
JID - 100885357
RN  - 1W21G5Q4N2 (Okadaic Acid)
SB  - IM
MH  - Analysis of Variance
MH  - *Aneuploidy
MH  - Animals
MH  - CHO Cells
MH  - Cell Division/drug effects
MH  - Chromosome Breakage
MH  - Chromosome Deletion
MH  - Cricetinae
MH  - Cricetulus
MH  - DNA Damage/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - In Situ Hybridization, Fluorescence
MH  - Liver/chemistry
MH  - Micronuclei, Chromosome-Defective/*drug effects
MH  - Micronucleus Tests
MH  - Okadaic Acid/pharmacokinetics/*toxicity
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2004/03/24 05:00
MHDA- 2004/08/13 05:00
CRDT- 2004/03/24 05:00
PHST- 2004/03/24 05:00 [pubmed]
PHST- 2004/08/13 05:00 [medline]
PHST- 2004/03/24 05:00 [entrez]
AID - 10.1002/tox.20004 [doi]
PST - ppublish
SO  - Environ Toxicol. 2004 Apr;19(2):123-8. doi: 10.1002/tox.20004.