Formation of the mutagenic DNA lesion 1,N2-ethenoguanine induced by heated cooking oil and identification of causative agents

• Published in: Genes and environment Vol. 45; no. 1; pp. 1 - 27
• Main Authors: Kasai, Hiroshi, Kawai, Kazuaki
• Format: Journal Article
• Language: English
• Published: Tokyo BioMed Central Ltd 25.10.2023; BioMed Central; BMC
• Subjects: 1,N2-ethenoguanine; 2,4-heptadienal; Adducts; Cancer; Carcinogenesis; Carcinogens; Cooking; Cooking oil; Cooking oils; Cosmetics industry; DDE; Deoxyribonucleic acid; DNA; DNA damage; Epoxy resins; Ethanol; Gastrointestinal carcinogenesis; Guanosines; Hemin; High performance liquid chromatography; Lipid peroxidation; Lipids; Liquid chromatography; Mass spectrometry; Nitrous oxide; Nucleosides; Oils and fats, Edible; Oxidation; Oxidative stress; Peroxidation; Physiological aspects; Reagents; Scientific imaging; Ultraviolet spectra; Vegetable oils; Japan
• ISSN: 1880-7062; 1880-7046; 1880-7062
• DOI: 10.1186/s41021-023-00284-3

The DNA-damaging compounds in heated cooking oil were identified as guanosine adducts. Heated vegetable oil was subjected to deep-frying conditions at 170 [degrees]C for 45 min, reacted with isopropylidene guanosine (ipG) at pH 7.4, and the resulting compounds were separated by high-performance liquid chromatography (HPLC). Two adducts, 8-hydroxy-ipG and 1,N.sup.2-etheno-ipG, were identified in the reaction mixture. One of the major components in heated cooking oil, 2,4-heptadienal (HDE), efficiently produced etheno-ipG from ipG in the presence of tBuOOH. An oxidized HDE solution was fractionated using HPLC to identify causative agents, and each fraction was tested for etheno-ipG formation. In addition to the known lipid peroxidation product, 4,5-epoxy-2-heptenal, two unknown polar components with potent etheno-ipG formation activity were discovered. Based on Mass and UV spectra, their structures were identified as 6-oxo- and 6-hydroxy-2,4-HDE. Similarly, 6-oxo- and 6-hydroxy-2,4- decadienal (DDE) were formed from 2,4-DDE. Significant amounts of 6-oxo- and 6-hydroxy-2,4-alkadienal were detected in the heated cooking oil. These compounds induced the formation of 1,N.sup.2-ethenoguanine in nucleosides and DNA, especially in the presence of tBuOOH. Moreover, the formation of 6-oxo- and 6-OH-HDE from 2,4-HDE was accelerated in the presence of hemin and tBuOOH. The results suggest that these compounds are not only generated during the oil heating process but also produced from 2,4-alkadienal through digestion under normal physiological conditions, especially after ingesting heme- and alkyl-OOH-containing diets. Moreover, these compounds can be formed within cells under oxidative stress, potentially linking them to gastrointestinal carcinogenesis.