An approach to cancer risk assessment for the food constituent 2-hexenal on the basis of 1,N²-propanodeoxyguanosine adducts of 2-hexenal in vivo

Abstract.

2-Hexenal is formed by plants, and humans are regularly exposed to this mutagenic/genotoxic compound via vegetable foods. 2-Hexenal has not been tested for carcinogenicity, but it forms exocyclic 1,N ^2-propanodeoxyguanosine adducts like other carcinogenic α,β-unsaturated carbonyl compounds. To quantify the respective DNA adducts as an approach to a theoretical cancer risk assessment, we used a newly developed ³²P-postlabelling technique based on nuclease P1 enrichment, allowing a detection limit of 3 adducts per 10⁸ nucleotides. Adduct levels were measured at different doses and the covalent binding index (CBI) was found to be dose-dependent. This can be explained by glutathione depletion at higher doses. The CBI at low doses was 0.06. A negligible cancer risk of 1–5 per 10⁷ lives was estimated on the basis of TD₅₀ values calculated from the correlation between CBI and TD₅₀ of Lutz and on the daily intake of 2-hexenal via vegetable foods, fruit juices and black tea. A risk of 1.6–8.5 per 10⁶ lives was estimated for the hypothetical case of glutathione depletion, e.g. due to consuming special medicaments. In every case, the benefit from eating fruit and vegetables is clearly higher than a possible low and unavoidable cancer risk. Utilization of 2-hexenal as a flavouring agent or as a fungicide, breeding fungus-resistant plants or technological gene construction of fungus resistance may lead to a high hypothetical cancer risk of 2–6 per 10⁴ lives under certain circumstances which are avoidable and deserves special case-by-case consideration.