ArticleChemico-biological interactions2013
Evidence for endogenous formation of the hepatocarcinogen N-nitrosodihydrouracil in rats treated with dihydrouracil and sodium nitrite: a potential source of human hepatic DNA carboxyethylation.
Article in Chemico-biological interactions, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 8 citations in OpenAlex.
- Salivary nitrate/nitrite and acetaldehyde in humans: potential combination effects in the upper gastrointestinal tract and possible consequences for the in vivo formation of N-nitroso compounds-a hypothesis.Archives of toxicology · 2022Article
- Quantitation by liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry of DNA adducts derived from methyl glyoxal and carboxyethylating agents in leukocytes of smokers and non-smokers.Chemico-biological interactions · 2020Article
- Dihydropyrimidinase protects from DNA replication stress caused by cytotoxic metabolites.Nucleic acids research · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
An earlier study demonstrated that hydrolysates of all human liver DNA samples analyzed contain the DNA adduct 7-(2'-carboxyethyl)guanine (7-CEGua) with an average level of 74.6 adducts per 10(9) nucleotides. One possible source of this DNA adduct would be endogenous nitrosation of the normal pyrimidine metabolites dihydrouracil (DHU) and β-ureidopropionic acid (β-UPA), yielding the corresponding nitroso compounds N-nitrosodihydrouracil, a potent hepatocarcinogen, and N-nitroso-β-ureidopropionic acid. Another potential source would be reaction of endogenously formed acrylic acid with DNA. We tested these hypotheses in a study in which rats were treated with NaNO2 in the drinking water, alone, or in combination with dietary DHU or β-UPA, or with acrylic acid in the drinking water, for either 2 or 4 weeks. Hepatic DNA from these rats was analyzed for 7-CEGua, using liquid chromatography-tandem mass spectrometry-selected reaction monitoring with confirmation by high resolution mass spectrometry. The results demonstrated consistent statistically significant increases of 7-CEGua in hepatic DNA of the rats treated with the combination of NaNO2 and DHU compared to the corresponding controls, while the other treatments gave variable results. These results support the hypothesis that endogenous nitrosation of DHU could be a major source of 7-CEGua in human hepatic DNA. Development of methodology for analysis of 7-CEGua in human leukocyte DNA is also reported, which will allow testing of this hypothesis in epidemiologic and clinical studies.
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