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Cytotoxic and genotoxic potential of food-borne nitriles in a liver in vitro model

View Article: PubMed Central - PubMed

ABSTRACT

Isothiocyanates are the most intensively studied breakdown products of glucosinolates from Brassica plants and well recognized for their pleiotropic effects against cancer but also for their genotoxic potential. However, knowledge about the bioactivity of glucosinolate-borne nitriles in foods is very poor. As determined by GC-MS, broccoli glucosinolates mainly degrade to nitriles as breakdown products. The cytotoxicity of nitriles in human HepG2 cells and primary murine hepatocytes was marginal as compared to isothiocyanates. Toxicity of nitriles was not enhanced in CYP2E1-overexpressing HepG2 cells. In contrast, the genotoxic potential of nitriles was found to be comparable to isothiocyanates. DNA damage was persistent over a certain time period and CYP2E1-overexpression further increased the genotoxic potential of the nitriles. Based on actual in vitro data, no indications are given that food-borne nitriles could be relevant for cancer prevention, but could pose a certain genotoxic risk under conditions relevant for food consumption.

No MeSH data available.


Analysis of cell viability in primary murine hepatocytes after a 72 hours treatment with nitriles using WST-1 assay.+: Positive control, 0.05% triton-X. Bars are mean + SEM, n ≥ 3. *P < 0.05; asterisks indicate a significant difference between the sample and the solvent control, medium.
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f4: Analysis of cell viability in primary murine hepatocytes after a 72 hours treatment with nitriles using WST-1 assay.+: Positive control, 0.05% triton-X. Bars are mean + SEM, n ≥ 3. *P < 0.05; asterisks indicate a significant difference between the sample and the solvent control, medium.

Mentions: To analyze the effect of nitriles on primary hepatocytes, allyl-CN, 3-butyl-CN, benzyl-CN, and 4-MTB-CN were studied in hepatocytes freshly isolated from mice. Allyl-CN, 3-but-CN and benzyl-CN significantly decreased the viability of hepatocytes in a concentration-dependent manner (Fig. 4) as analyzed by WST-1 assay after 72 h of exposure. This loss in cell viability was higher for allyl-CN and 3-but-CN than in HepG2 cells (Fig. 2A). For 4-MTB-CN, a viability loss was detected only at 30 mM, comparable with the effect in HepG2 cells (Fig. 2C).


Cytotoxic and genotoxic potential of food-borne nitriles in a liver in vitro model
Analysis of cell viability in primary murine hepatocytes after a 72 hours treatment with nitriles using WST-1 assay.+: Positive control, 0.05% triton-X. Bars are mean + SEM, n ≥ 3. *P < 0.05; asterisks indicate a significant difference between the sample and the solvent control, medium.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121622&req=5

f4: Analysis of cell viability in primary murine hepatocytes after a 72 hours treatment with nitriles using WST-1 assay.+: Positive control, 0.05% triton-X. Bars are mean + SEM, n ≥ 3. *P < 0.05; asterisks indicate a significant difference between the sample and the solvent control, medium.
Mentions: To analyze the effect of nitriles on primary hepatocytes, allyl-CN, 3-butyl-CN, benzyl-CN, and 4-MTB-CN were studied in hepatocytes freshly isolated from mice. Allyl-CN, 3-but-CN and benzyl-CN significantly decreased the viability of hepatocytes in a concentration-dependent manner (Fig. 4) as analyzed by WST-1 assay after 72 h of exposure. This loss in cell viability was higher for allyl-CN and 3-but-CN than in HepG2 cells (Fig. 2A). For 4-MTB-CN, a viability loss was detected only at 30 mM, comparable with the effect in HepG2 cells (Fig. 2C).

View Article: PubMed Central - PubMed

ABSTRACT

Isothiocyanates are the most intensively studied breakdown products of glucosinolates from Brassica plants and well recognized for their pleiotropic effects against cancer but also for their genotoxic potential. However, knowledge about the bioactivity of glucosinolate-borne nitriles in foods is very poor. As determined by GC-MS, broccoli glucosinolates mainly degrade to nitriles as breakdown products. The cytotoxicity of nitriles in human HepG2 cells and primary murine hepatocytes was marginal as compared to isothiocyanates. Toxicity of nitriles was not enhanced in CYP2E1-overexpressing HepG2 cells. In contrast, the genotoxic potential of nitriles was found to be comparable to isothiocyanates. DNA damage was persistent over a certain time period and CYP2E1-overexpression further increased the genotoxic potential of the nitriles. Based on actual in vitro data, no indications are given that food-borne nitriles could be relevant for cancer prevention, but could pose a certain genotoxic risk under conditions relevant for food consumption.

No MeSH data available.