Detection of 1,N-2-propanodeoxyguanosine adducts of 2-hexenal in organs ofFischer 344 rats by a P-32-post-labeling technique

2-Hexenal is an ate-unsaturated carbonyl compound which is mutagenic, genot oxic and forms cyclic 1,N-2-propanodeoxyguanosine adducts like similar prop enals for which carcinogenicity was shown, e.g. acrolein or crotonaldehyde, Since humans have a permanent intake of 2-hexenal via vegetarian food this genotoxic compound is considered to play a role in human carcinogenicity, The data base is, however, presently not sufficient for a cancer risk asses sment. To date no long term carcinogenicity study on 2-hexenal has been pub lished. Detection of respective DNA adducts of this substance in animals or humans could allow cancer risk assessment, Therefore, we have developed a P-32-post-labeling technique based on nuclease P1 enrichment and TLC separa tion of the labeled adducts, The respective adducts are stable over a wide pH range from pH 4 to pH 11 and relatively stable against nuclease P1, The detection limit was 0.03 adducts per 10(6) nucleotides and the recovery was 10%. With this method we have shown ill vivo formation of 1,N-2-propanodeo syguanosine adducts of 2-hexenal for the first time and found the respectiv e DNA adducts in different organs of Fischer 344 rats after gavage of 500, 200 and 50 mg 2-hexenal/kg body wt. No adducts could be detected in the org ans of untreated rats. There is a clear dependence of the adduct level and the CBI (covalent binding index) on the dose. The CBI of 2-hexenal calculat ed on the basis of our adduct levels is extremely low (0.06), Since intake of 2-hexenal via fruit and vegetables is very Low the cancer risk from 2-he xenal intake via food must also be considered as very low according to a fi rst raw estimation on the basis of CBI and intake. The situation deserves, however, a more precise risk assessment in the future.