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Transcriptomic comparison of cyanotoxin variants in a human intestinal model revealed major differences in oxidative stress response: Effects of MC-RR and MC-LR on Caco-2 cells
- Source :
- Ecotoxicology and Environmental Safety, Ecotoxicology and Environmental Safety, Elsevier, 2012, epub ahead of print. ⟨10.1016/j.ecoenv.2012.05.001⟩
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- Microcystins (MCs) are cyclic hepatotoxins produced by various species of cyanobacteria. Their structure includes two variable amino acids (AA) giving rise to more than 90 MC variants, however most of the studies to date have focused on the most toxic variant: microcystin LR (MC-LR). Ingestion is the major route of human exposure to MCs and several in vivo studies have demonstrated macroscopic effects on the gastro-intestinal tract. However, little information exists concerning the pathways affected by MC variants on intestinal cells. In the current study, we have investigated the effects of MC-RR and MC-LR on the human intestinal cell line Caco-2 using a non-selective method and compared their response at the pangenomic scale. The cells were incubated for 4h or 24h with a range of non-toxic concentrations of MC-RR or MC-LR. Minimal effects were observed after short term exposures (4h) to either MC variant. In contrast, dose dependent modulations of gene transcription levels were observed with MC-RR and MC-LR after 24h. The transcriptomic profiles induced by MC-RR were quite similar to those induced by MC-LR, suggestive of a largely common mechanism of toxicity. However, changes in total gene expression were more pronounced following exposure to MC-LR compared to MC-RR, as revealed by functional annotation. MC-LR affected two principal pathways, the oxidative stress response and cell cycle regulation, which did not elicit significant alteration following MC-RR exposure. This work is the first comparative description of the effects of MC-LR and MC-RR in a human intestinal cell model at the pangenomic scale. It has allowed us to propose differences in the mechanism of toxicity for MC-RR and MC-LR. These results illustrate that taking into account the toxicity of MC variants remains a key point for risk assessment.
- Subjects :
- Microcystins
Health, Toxicology and Mutagenesis
Microcystin-LR
Biology
Bioinformatics
Transcriptome
03 medical and health sciences
chemistry.chemical_compound
In vivo
Humans
caco-2 cell
030304 developmental biology
0303 health sciences
model
cyanotoxin
Gene Expression Profiling
030302 biochemistry & molecular biology
Public Health, Environmental and Occupational Health
toxicologie
General Medicine
Cell cycle
Pollution
Molecular biology
3. Good health
Gene expression profiling
Oxidative Stress
Gene Expression Regulation
chemistry
Caco-2
[SDV.TOX]Life Sciences [q-bio]/Toxicology
Toxicity
Marine Toxins
Caco-2 Cells
Marine toxin
Subjects
Details
- ISSN :
- 01476513 and 10902414
- Volume :
- 82
- Database :
- OpenAIRE
- Journal :
- Ecotoxicology and Environmental Safety
- Accession number :
- edsair.doi.dedup.....d459b36091e46f68be4665dadb6538f9