ArticleMutagenesis2017
Pyridylhydroxybutyl and pyridyloxobutyl DNA phosphate adduct formation in rats treated chronically with enantiomers of the tobacco-specific nitrosamine metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol.
Article in Mutagenesis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- Mass Spectrometry-Based Metabolic Profiling of Urinary Metabolites ofChemical research in toxicology · 2023Article
- DNA Alkylation Damage by Nitrosamines and Relevant DNA Repair Pathways.International journal of molecular sciences · 2023Review
- Metabolism and DNA Adduct Formation of Tobacco-SpecificInternational journal of molecular sciences · 2022Review
- Identification of anChemical research in toxicology · 2021Article
- Investigation of 2'-Deoxyadenosine-Derived Adducts Specifically Formed in Rat Liver and Lung DNA byChemical research in toxicology · 2021Article
- Methyl DNA phosphate adduct formation in lung tumor tissue and adjacent normal tissue of lung cancer patients.Carcinogenesis · 2019Article
- Physical binding of the tobacco smoke carcinogen NNK diazonium ion to the human tumor suppressor gene TP53 Exon 5.Toxicology research · 2019Article
- Mass Spectrometric Quantitation of Pyridyloxobutyl DNA Phosphate Adducts in Rats Chronically Treated with N'-Nitrosonornicotine.Chemical research in toxicology · 2019Article
- Quantification of DNA Lesions Induced by 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Mammalian Cells.Chemical research in toxicology · 2019Article
- Review
- Formalin-Fixed Paraffin-Embedded Tissues-An Untapped Biospecimen for Biomonitoring DNA Adducts by Mass Spectrometry.Toxics · 2018Review
- Analysis and Identification of 2'-Deoxyadenosine-Derived Adducts in Lung and Liver DNA of F-344 Rats Treated with the Tobacco-Specific Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone and Enantiomers of its Metabolite 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol.Chemical research in toxicology · 2018Article
- Methyl DNA Phosphate Adduct Formation in Rats Treated Chronically with 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone and Enantiomers of Its Metabolite 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol.Chemical research in toxicology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is metabolically converted to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in a reaction which is both stereoselective and reversible. NNAL is also a lung carcinogen, with both (R)-NNAL and (S)-NNAL inducing a high incidence of lung tumours in rats. Both NNAL and NNK undergo metabolic activation to intermediates which react with DNA to form pyridylhydroxybutyl and pyridyloxobutyl DNA adducts, respectively. DNA adduct formation by NNAL and NNK is an important step in their mechanisms of carcinogenesis. In this study, we quantified both pyridylhydroxybutyl and pyridyloxobutyl DNA phosphate adducts in the lung of rats treated with 5 ppm of (R)-NNAL or (S)-NNAL in drinking water for 10, 30, 50 and 70 weeks. In (R)-NNAL-treated rats, the pyridylhydroxybutyl and pyridyloxobutyl phosphate adducts were 4530-6920 fmol/mg DNA and 46-175 fmol/mg DNA, accounting for 45-51% and 0.3-1% of the total measured DNA phosphate and base adducts, respectively. In (S)-NNAL-treated rats, the two types of phosphate adducts were 3480-4180 fmol/mg DNA and 1180-4650 fmol/mg DNA, accounting for 30-36% and 11-38% of the total adducts, respectively. Distinct patterns of adduct formation were observed, with higher levels of NNAL-derived pyridylhydroxybutyl phosphate adducts and lower levels of NNK-derived pyridyloxobutyl phosphate adducts in the (R)-NNAL treatment group than the (S)-NNAL group. The persistence and increase over time of certain pyridylhydroxybutyl phosphate adducts over the course of the study suggest that these adducts could be useful biomarkers of chronic exposure to NNAL and NNK. The results of this study provide important new information regarding DNA damage by NNAL and NNK, and contribute to understanding mechanisms of tobacco-related carcinogenesis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.