International audience | Aflatoxin B1 (AFB1) is the most potent natural carcinogen among mycotoxins. Versicolorin A (VerA) is a precursor of AFB1 biosynthesis and is structurally related to the latter. Although VerA has already been identified as a genotoxin, data on the toxicity of VerA are still scarce, especially at low concentrations. The SOS/umu and miniaturised version of the Ames test in Salmonella Typhimurium strains used in the present study shows that VerA induces point mutations. This effect, like AFB1, depends primarily on metabolic activation of VerA. VerA also induced chromosomal damage in metabolically competent intestinal cells (IPEC-1) detected by the micronucleus assay. Furthermore, results from the standard and enzyme-modified comet assay confirmed the VerA-mediated DNA damage, and we observed that DNA repair pathways were activated upon exposure to VerA, as indicated by the phosphorylation and/or relocation of relevant DNA-repair biomarkers (γH2AX and 53BP1/FANCD2, respectively). In conclusion, VerA induces DNA damage without affecting cell viability at concentrations as low as 0.03 μM, highlighting the danger associated with VerA exposure and calling for more research on the carcinogenicity of this emerging food contaminant.

Aflatoxin B1 (AFB1) is the most potent natural carcinogen among mycotoxins. Versicolorin A (VerA) is a precursor of AFB1 biosynthesis and is structurally related to the latter. Although VerA has already been identified as a genotoxin, data on the toxicity of VerA are still scarce, especially at low concentrations. The SOS/umu and miniaturised version of the Ames test in Salmonella Typhimurium strains used in the present study shows that VerA induces point mutations. This effect, like AFB1, depends primarily on metabolic activation of VerA. VerA also induced chromosomal damage in metabolically competent intestinal cells (IPEC-1) detected by the micronucleus assay. Furthermore, results from the standard and enzyme-modified comet assay confirmed the VerA-mediated DNA damage, and we observed that DNA repair pathways were activated upon exposure to VerA, as indicated by the phosphorylation and/or relocation of relevant DNA-repair biomarkers (γH2AX and 53BP1/FANCD2, respectively). In conclusion, VerA induces DNA damage without affecting cell viability at concentrations as low as 0.03 μM, highlighting the danger associated with VerA exposure and calling for more research on the carcinogenicity of this emerging food contaminant.

Telomeres protect the coding sequence of chromosome ends and Telomere Length (TL) has been proposed as a biomarker of cellular aging, cumulative stress exposure and life-span in humans. With the aim to propose new biomarkers, a q-PCR protocol was adapted for the measurement of TL in the European flounder Platichthys flesus. The protocol was then applied in 2-year-old flounders from the Seine Estuary. The absolute TL in the flounder is 54 ± 13 kbp per genome (mean ± standard error). Considering relative or absolute TL, no correlation was observed with DNA damage and any of the measured contaminant concentrations (trace elements, metabolites of polycyclic aromatic hydrocarbons, polychlorobiphenyls, organochlorinated pesticides, polybrominated diphenyl ethers, perfluoroalkyl substances). Because sampling was limited, further investigations are required to state a possible impact of chemical pollution on flatfish telomeres. This is motivated by correlations observed with organochlorinated compounds when decreasing statistical significance (p ≤ 0.10).

A multibiomarker approach was developed to evaluate the juvenile European flounder responses to a complex mixture of 9 polycyclic aromatic hydrocarbons (PAHs) and 12 polychlorinated biphenyls (PCBs). Exposure was performed through contaminated food pellets displaying: (1) PAH and PCB levels similar to those detected in the heavily polluted Seine estuary, respectively in sediments and in flatfish and (2) ten times these concentrations. Several biomarkers of the immune system (e.g., lysozyme concentration and gene expression of complement component C3 and TNF-receptor), DNA damage (e.g., Comet assay), energetic metabolism (e.g., activity of cytochrome C oxidase), detoxification process (e.g., cytochrome P450 1A1 expression level: CYP1A1; betaine homocysteine methyl transferase expression level: BHMT) were investigated after 14 and 29 days of contamination, followed by a 14-days recovery period. After 29 days of contamination, the detoxification activity (CYP1A1 expression level) was positively correlated with DNA damages; the increase of the BHMT expression level could also be related to the detoxification process. Furthermore, after the recovery period, some biomarkers were still upregulated (i.e., CYP1A1 and BHMT expression levels). The immune system was significantly modulated by the chemical stress at the two concentration levels, and the lysozyme appeared to be the most sensitive marker of the mixture impact.

Recently, research has contributed to better knowledge on the occurrence of pesticides in coastal water by identifying frequently detected substances, their concentration range and their acute and chronic toxicity for organisms. Pesticide pollution is of particular concern in France due to important agricultural activities and presence of several exoreic catchment areas that vehicle pesticides up to coastal waters, impacting non-target marine species. Several ecotoxicology questions remain to be addressed concerning the long-term effects of chronic pesticide exposure and the mechanisms involved in adaptation to chemical stress. In the present study, we brought new insights on the genetic and epigenetic effects of the herbicide diuron in oyster genitors. During gametogenesis, we exposed Crassostrea gigas to environmentally realistic herbicide concentrations (0.2–0.3 μg L−1 during two 7-day periods at half-course and end of gametogenesis). Diuron exposure was shown to decrease global DNA methylation and total methyltransferase activity in whole oyster tissue; this is consistent with the previous observation of a significant decrease in DNMT1 gene expression. Diuron effect seemed to be tissue-specific; hypermethylation was detected in the digestive gland, whereas diuron exposure had no effect on gill and gonad tissue. The genotoxicity of diuron was confirmed by the detection of one adduct in gonad DNA. By using in vitro approaches and human DNMT1 (DNMT1 has not been purified yet in bivalves), the presence of DNA lesions (adduct, 8-oxodGuo) was shown to interfere with DNMT1 activity, indicating a complex interaction between DNA damage and DNA methylation. Based on our results, we propose mechanisms to explain the effect of diuron exposure on DNA methylation, a widespread epigenetic mark.