In vitro and in silico study on consequences of combined exposure to the food-borne alkenylbenzenes estragole and safrole

Potential consequences of combined exposure to the selected food-borne alkenylbenzenes safrole and estragole or their proximate carcinogenic 1'-hydroxy metabolites were evaluated in vitro and in silico. HepG2 cells were exposed to 1'-hydroxyestragole and 1'-hydroxysafrole individually or in equipotent combination subsequently detecting cytotoxicity and DNA adduct formation. Results indicate that concentration addition adequately describes the cytotoxic effects and no statistically significant differences were shown in the level of formation of the major DNA adducts. Furthermore, physiologically based kinetic modeling revealed that at normal dietary intake the concentration of the parent compounds and their 1'-hydroxymetabolites remain substantially below the Km values for the respective bioactivation and detoxification reactions providing further support for the fact that the simultaneous presence of the two carcinogens or of their proximate carcinogenic 1'-hydroxy metabolites may not affect their DNA adduct formation. Overall, these results point at the absence of interactions upon combined exposure to selected food-borne alkenylbenzenes at realistic dietary levels of intake.

Automated summary

The study evaluated the potential consequences of combined exposure to safrole and estragole or their proximate carcinogenic metabolites in vitro and in silico. Results showed that concentration addition adequately described the cytotoxic effects and there were no significant differences in the level of formation of DNA adducts. Furthermore, physiologically based kinetic modeling indicated that the concentration of the parent compounds and their metabolites remained below the Km values for bioactivation and detoxification reactions at normal dietary intake levels, suggesting that combined exposure to these carcinogenic compounds may not affect DNA adduct formation.