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.
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,N2-propanodeoxyguanosine adducts like other carcinogenic alpha,beta-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 10(8) 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 10(7) 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 10(6) 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 10(4) lives under certain circumstances which are avoidable and deserves special case-by-case consideration.
Eder
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Department of Toxicology, University of Würzburg, Germany. eder@toxi.uni-wuerzburg.de
Schuler
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D000284:Administration, Oral; D000447:Aldehydes / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001345:Autoradiography; D002273:Carcinogens / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D002846:Chromatography, Affinity; D004247:DNA / Q000187:drug effects; D018736:DNA Adducts / Q000032:analysis*; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005506:Food Contamination / Q000032:analysis*; D008297:Male; D010761:Phosphorus Radioisotopes; D051381:Rats; D011916:Rats, Inbred F344; D018570:Risk Assessment
D000447:Aldehydes; D002273:Carcinogens; D018736:DNA Adducts; D010761:Phosphorus Radioisotopes; C060934:1,N(2)-propanodeoxyguanosine; C051750:2-hexenal; D004247:DNA; D003849:Deoxyguanosine