Detection of 1,N2-propanodeoxyguanosine adducts of 2-hexenal in organs of Fischer 344 rats by a 32P-post-labeling technique.

Abstract

2-Hexenal is an alpha,beta-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 10(6) 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.

• Authors: D Schuler, E Eder
• Journal: Carcinogenesis (Carcinogenesis) Vol. 20 Issue 7 Pg. 1345-50 (Jul 1999) ISSN: 0143-3334 [Print] England
• PMID: 10383910 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aldehydes
• DNA Adducts
• Phosphorus Radioisotopes
• 1,N(2)-propanodeoxyguanosine
• 2-hexenal
• Deoxyguanosine

Topics

• Aldehydes (metabolism, pharmacology)
• Animals
• Chromatography, High Pressure Liquid
• Chromatography, Thin Layer
• DNA Adducts (metabolism)
• Deoxyguanosine (analogs & derivatives, metabolism)
• Dose-Response Relationship, Drug
• Esophagus (metabolism)
• Gastric Mucosa (metabolism)
• Liver (metabolism)
• Magnetic Resonance Spectroscopy
• Male
• Phosphorus Radioisotopes
• Rats
• Rats, Inbred F344
• Tissue Distribution