Journal Article

Detection of 1,<i>N</i><sup>2</sup>-propanodeoxyguanosine adducts of 2-hexenal in organs of Fischer 344 rats by a <sup>32</sup>P-post-labeling technique

Detlef Schuler and Erwin Eder

in Carcinogenesis

Volume 20, issue 7, pages 1345-1350
Published in print July 1999 | ISSN: 0143-3334
Published online July 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.7.1345
Detection of 1,N2-propanodeoxyguanosine adducts of 2-hexenal in organs of Fischer 344 rats by a 32P-post-labeling technique

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2-Hexenal is an α,β-unsaturated carbonyl compound which is mutagenic, genotoxic and forms cyclic 1,N2-propanodeoxyguanosine adducts like similar propenals 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 assessment. To date no long term carcinogenicity study on 2-hexenal has been published. Detection of respective DNA adducts of this substance in animals or humans could allow cancer risk assessment. Therefore, we have developed a 32P-post-labeling technique based on nuclease P1 enrichment and TLC separation 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 106 nucleotides and the recovery was 10%. With this method we have shown in vivo formation of 1,N 2-propanodeoxyguanosine adducts of 2-hexenal for the first time and found the respective 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 organs 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 calculated 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-hexenal intake via food must also be considered as very low according to a first raw estimation on the basis of CBI and intake. The situation deserves, however, a more precise risk assessment in the future.

Keywords: 3′-dGp, deoxyguanosine-3′-monophosphate; CBI, covalent binding index; dG, deoxyguanosine; F344 rats, Fischer 344 rats; Hex-dGp, deoxyguanosine 3′-monophosphate adduct of 2-hexenal (for structure see Figure 1c for IUPAC nomenclature and structural features see Results); Hex-pdGp, deoxyguanosine 3′-,5′-bisphosphate adduct of 2-hexenal; PEI, polyethylene imine; RP, reverse phase.

Journal Article.  5289 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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