Limits...
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 DNA strand breaks of CYP2E1 transfected HepG2 and vector cells, treated with benzyl-CN and benzyl-ITC for 24 hours using the Comet assay.Data are presented as mean + SEM. to corresponding control, for nitriles medium (solvent), for benzyl-ITC and B[α]P 0.1% DMSO (solvent), B[α]P 50 μM: Benzo[a]pyrene, positive control, n = 3, *P ≤ 0.05 significance is related to the solvent control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5121622&req=5

f6: Analysis of DNA strand breaks of CYP2E1 transfected HepG2 and vector cells, treated with benzyl-CN and benzyl-ITC for 24 hours using the Comet assay.Data are presented as mean + SEM. to corresponding control, for nitriles medium (solvent), for benzyl-ITC and B[α]P 0.1% DMSO (solvent), B[α]P 50 μM: Benzo[a]pyrene, positive control, n = 3, *P ≤ 0.05 significance is related to the solvent control.

Mentions: Risk-benefit evaluation of bioactive compounds formed in Brassica vegetables is not only based on its cancer preventive potency, but also on further aspects such as genotoxicity15. ITC are comparatively electrophilic compounds that have been shown to act genotoxic, at least in vitro1920. Representatively, the genotoxicity was investigated in terms of DNA break induction for 4-MTB-CN and benzyl-CN in comparison to benzyl-ITC using the Comet assay (Fig. 5). 4-MTB-CN and benzyl-CN induced a concentration-dependent increase in DNA strand breaks as determined by the Olive Tail Moment and percent tail DNA (Fig. 5A and B). A significant increase in DNA strand breaks was evident for 4-MTB-CN and benzyl-CN at a concentration of ≥3 μM. The DNA damage induced by 3 μM benzyl-CN was then comparable with the effect of benzyl ITC at the same concentration (Fig. 5A and B). After 24 h of recovery, the DNA damage still persisted (Fig. 5C and D). Analog to the cytotoxicity tests, next the effect of CYP2E1 expression on the genotoxic potency of nitriles was analyzed (Fig. 6). CYP2E1-overexpression caused a significant increment of DNA strand breaks at concentrations of ≥3 μM benzyl-CN as compared to vector control cells. This indicates a relevance of CYP2E1 for the genotoxic potential of this nitrile.


Cytotoxic and genotoxic potential of food-borne nitriles in a liver in vitro model
Analysis of DNA strand breaks of CYP2E1 transfected HepG2 and vector cells, treated with benzyl-CN and benzyl-ITC for 24 hours using the Comet assay.Data are presented as mean + SEM. to corresponding control, for nitriles medium (solvent), for benzyl-ITC and B[α]P 0.1% DMSO (solvent), B[α]P 50 μM: Benzo[a]pyrene, positive control, n = 3, *P ≤ 0.05 significance is related to the solvent control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Analysis of DNA strand breaks of CYP2E1 transfected HepG2 and vector cells, treated with benzyl-CN and benzyl-ITC for 24 hours using the Comet assay.Data are presented as mean + SEM. to corresponding control, for nitriles medium (solvent), for benzyl-ITC and B[α]P 0.1% DMSO (solvent), B[α]P 50 μM: Benzo[a]pyrene, positive control, n = 3, *P ≤ 0.05 significance is related to the solvent control.
Mentions: Risk-benefit evaluation of bioactive compounds formed in Brassica vegetables is not only based on its cancer preventive potency, but also on further aspects such as genotoxicity15. ITC are comparatively electrophilic compounds that have been shown to act genotoxic, at least in vitro1920. Representatively, the genotoxicity was investigated in terms of DNA break induction for 4-MTB-CN and benzyl-CN in comparison to benzyl-ITC using the Comet assay (Fig. 5). 4-MTB-CN and benzyl-CN induced a concentration-dependent increase in DNA strand breaks as determined by the Olive Tail Moment and percent tail DNA (Fig. 5A and B). A significant increase in DNA strand breaks was evident for 4-MTB-CN and benzyl-CN at a concentration of ≥3 μM. The DNA damage induced by 3 μM benzyl-CN was then comparable with the effect of benzyl ITC at the same concentration (Fig. 5A and B). After 24 h of recovery, the DNA damage still persisted (Fig. 5C and D). Analog to the cytotoxicity tests, next the effect of CYP2E1 expression on the genotoxic potency of nitriles was analyzed (Fig. 6). CYP2E1-overexpression caused a significant increment of DNA strand breaks at concentrations of ≥3 μM benzyl-CN as compared to vector control cells. This indicates a relevance of CYP2E1 for the genotoxic potential of this nitrile.

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.