Combined effects of okadaic acid and cadmium on lipid peroxidation and DNA bases modifications (m5dC and 8-(OH)-dG) in Caco-2 cells

被引:35
作者
Traoré, A
Ruiz, S
Baudrimont, I
Sanni, A
Dano, SD
Guarigues, P
Narbonne, JF
Creppy, EE
机构
[1] Univ Bordeaux 2, Dept Toxicol, F-33076 Bordeaux, France
[2] Toxicol Lab, Bordeaux 1, France
[3] Univ Natl Benin, FAST, Dept Biochim & Biol Cellulaire, Cotonou, Benin
[4] Univ Abidjan, Fac Pharm, Abidjan, Cote Ivoire
关键词
okadaic acid; cadmium; Caco-2; cells; lipid peroxidation; malondialdehyde; 5-methyldeoxycytosine and 8-hydroxydeoxyguanosine;
D O I
10.1007/s002040050656
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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 m(5)dC/(dC + m(5)dC) 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 mu g/ml) for 24 h, protein synthesis was inhibited (by 42 +/- 5%, 18 +/- 13%, and 90 +/- 4% respectively) while MDA production was 2235 +/- 129, 1710 +/- 20, and 11496 +/- 1624 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 (16874 +/- 2189 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.
引用
收藏
页码:79 / 84
页数:6
相关论文
共 42 条
[21]  
HIDALGO IJ, 1989, GASTROENTEROLOGY, V96, P736
[22]   NEURON AND GLIAL-CELL MARKER PROTEINS AS INDICATORS OF HEAVY METAL-INDUCED NEUROTOXICITY IN NEUROBLASTOMA AND GLIOMA CELL-LINES [J].
HUANG, J ;
TANII, H ;
KATO, K ;
HASHIMOTO, K .
ARCHIVES OF TOXICOLOGY, 1993, 67 (07) :491-496
[23]  
*IARC, 1999, IARC MON, V1
[24]   Metallothionein: An intracellular protein to protect against cadmium toxicity [J].
Klaassen, CD ;
Liu, J ;
Choudhuri, S .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1999, 39 :267-294
[25]   DNA methylation, heterochromatin and epigenetic carcinogens [J].
Klein, CB ;
Costa, M .
MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH, 1997, 386 (02) :163-180
[26]   Apoptosis and mitotic arrest are two independent effects of the protein phosphatases inhibitor okadaic acid in K562 leukemia cells [J].
Lerga, A ;
Richard, C ;
Delgado, MD ;
Cañelles, M ;
Frade, P ;
Cuadrado, MA ;
León, J .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 260 (01) :256-264
[27]   Okadaic acid-induced lens epithelial cell apoptosis requires inhibition of phosphatase-1 and is associated with induction of gene expression including p53 and bax [J].
Li, DWC ;
Fass, U ;
Huizar, I ;
Spector, A .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1998, 257 (02) :351-361
[28]   Comparison of the formation of 8-hydroxy-2′-deoxyguanosine and single- and double-strand breaks in DNA mediated by Fenton reactions [J].
Lloyd, DR ;
Carmichael, PL ;
Phillips, DH .
CHEMICAL RESEARCH IN TOXICOLOGY, 1998, 11 (05) :420-427
[29]   ENDOGENOUS DNA-ADDUCTS - POTENTIAL AND PARADOX [J].
MARNETT, LJ ;
BURCHAM, PC .
CHEMICAL RESEARCH IN TOXICOLOGY, 1993, 6 (06) :771-785
[30]   Oxygen reactive radicals production in cell culture by okadaic acid and their implication in protein synthesis inhibition [J].
Matias, WG ;
Traore, A ;
Bonini, M ;
Sanni, A ;
Creppy, EE .
HUMAN & EXPERIMENTAL TOXICOLOGY, 1999, 18 (10) :634-639