| Combined effects of okadaic acid and cadmium on lipid peroxidation and DNA bases modifications (m5dC and 8-(OH)-dG) in Caco-2 cells. | |
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MedLine Citation:
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PMID: 10839474 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Okadaic acid (OA) is a marine toxin, a tumour promoter and an inducer of apoptosis. It mainly inhibits protein-phosphatases, protein synthesis and enhances lipid peroxidation. Cadmium (Cd) is known to be carcinogenic in animals and humans (group 1 according to the International Agency for Research on Cancer (IARC) classification). Cd also induces oxidative stress in living organisms. Since they are sometimes found simultaneously in mussels, we have evaluated in the present investigation, the lipid peroxidation, as malondialdehyde (MDA) production, in the variation of the ratios of 8-(OH)-dG/10(5)dG and m5dC/(dC + m5dC) induced by OA and/or Cd in Caco-2 cells. When cells were treated exclusively by OA (15 ng/ml) or Cd (0.625 and 5 microg/ml) for 24 h, protein synthesis was inhibited (by 42 +/- 5%, 18 +/- 13%, and 90 +/- 4% respectively) while MDA production was 2,235 +/- 129, 1710 +/- 20, and 11,496 +/-1,624 pmol/mg protein respectively. In addition, each toxicant induced modified bases in DNA; increases in oxidised bases and methylated dC. The combination of OA and cadmium was more cytotoxic and caused more DNA base modifications; the ratio m(5)dC/(m(5)dC + dC) was increased from 3 +/- 0.15 to 9 +/- 0.15 and the ratio 8-(OH)-dG/10(5) dG also (from 36 +/- 2 to 76 +/- 6). The combination of OA and Cd also increased the level of MDA (1,6874 +/- 2,189 pmole/mg protein). The present results strongly suggest that DNA damage resulting from the oxidative stress induced by these two toxicants may significantly contribute to increasing their carcinogenicity via epigenetic processes. |
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Authors:
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A Traoré; S Ruiz; I Baudrimont; A Sanni; S D Dano; P Guarigues; J F Narbonne; E E Creppy |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Archives of toxicology Volume: 74 ISSN: 0340-5761 ISO Abbreviation: Arch. Toxicol. Publication Date: 2000 Apr |
Date Detail:
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Created Date: 2000-08-17 Completed Date: 2000-08-17 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0417615 Medline TA: Arch Toxicol Country: GERMANY |
Other Details:
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Languages: eng Pagination: 79-84 Citation Subset: IM |
Affiliation:
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Department of Toxicology, University Victor Segalen Bordeaux 2, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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5-Methylcytosine
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analogs & derivatives Caco-2 Cells / drug effects, metabolism Cadmium / toxicity* Carcinogens / toxicity* Chromatography, High Pressure Liquid Cytosine / analogs & derivatives, metabolism DNA / drug effects*, metabolism Deoxyguanosine / analogs & derivatives, metabolism Drug Synergism Enzyme Inhibitors / toxicity* Humans Leucine / metabolism Lipid Peroxidation / drug effects* Malondialdehyde / metabolism Okadaic Acid / toxicity* Protein Synthesis Inhibitors / toxicity |
| Chemical | |
Reg. No./Substance:
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0/5-methyldeoxycytosine; 0/8-hydroxy-2'-deoxyguanosine; 0/Carcinogens; 0/Enzyme Inhibitors; 0/Protein Synthesis Inhibitors; 542-78-9/Malondialdehyde; 554-01-8/5-Methylcytosine; 61-90-5/Leucine; 71-30-7/Cytosine; 7440-43-9/Cadmium; 78111-17-8/Okadaic Acid; 9007-49-2/DNA; 961-07-9/Deoxyguanosine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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