ArticleToxicological sciences : an official journal of the Society of Toxicology2013
Influence of DNA repair on nonlinear dose-responses for mutation.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 68 citations in OpenAlex.
- Biological Basis for Threshold Responses to Methylating Agents.Chemical research in toxicology · 2020Review
- Occurrence and repair of alkylating stress in the intracellular pathogen Brucella abortus.Nature communications · 2019Article
- Understanding the importance of low-molecular weight (ethylene oxide- and propylene oxide-induced) DNA adducts and mutations in risk assessment: Insights from 15 years of research and collaborative discussions.Environmental and molecular mutagenesis · 2019Review
- Goodbye to the bioassay.Toxicology research · 2018Review
- Benchmark dose analyses of multiple genetic toxicity endpoints permit robust, cross-tissue comparisons of MutaMouse responses to orally delivered benzo[a]pyrene.Archives of toxicology · 2018Article
- Uptake of glucose-conjugated MGMT inhibitors in cancer cells: role of flippases and type IV P-type ATPases.Scientific reports · 2017Article
- A threshold of endogenous stress is required to engage cellular response to protect against mutagenesis.Scientific reports · 2016Article
- Setting Occupational Exposure Limits for Genotoxic Substances in the Pharmaceutical Industry.Toxicological sciences : an official journal of the Society of Toxicology · 2016Review
- The clastogenicity of 4NQO is cell-type dependent and linked to cytotoxicity, length of exposure and p53 proficiency.Mutagenesis · 2016Article
- Synergistic and Antagonistic Mutation Responses of Human MCL-5 Cells to Mixtures of Benzo[a]pyrene and 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]pyridine: Dose-Related Variation in the Joint Effects of Common Dietary Carcinogens.Environmental health perspectives · 2016Article
- Sublinear response in lacZ mutant frequency of Muta™ Mouse spermatogonial stem cells after low dose subchronic exposure to N-ethyl-N-nitrosourea.Environmental and molecular mutagenesis · 2015Article
- Profiling dose-dependent activation of p53-mediated signaling pathways by chemicals with distinct mechanisms of DNA damage.Toxicological sciences : an official journal of the Society of Toxicology · 2014Article
- Derivation of point of departure (PoD) estimates in genetic toxicology studies and their potential applications in risk assessment.Environmental and molecular mutagenesis · 2014Article
- The endogenous exposome.DNA repair · 2014Review
- Complete protection against aflatoxin B(1)-induced liver cancer with a triterpenoid: DNA adduct dosimetry, molecular signature, and genotoxicity threshold.Cancer prevention research (Philadelphia, Pa.) · 2014Article
- Automation and validation of micronucleus detection in the 3D EpiDerm™ human reconstructed skin assay and correlation with 2D dose responses.Mutagenesis · 2014Article
- Molecular dosimetry of endogenous and exogenous O(6)-methyl-dG and N7-methyl-G adducts following low dose [D3]-methylnitrosourea exposures in cultured human cells.Chemical research in toxicology · 2014Article
- Using Various Nonlinear Response Surfaces for Mathematical Description of the Type of Combined Toxicity.Dose-response : a publication of International Hormesis SocietyArticle
- Contributions of DNA repair and damage response pathways to the non-linear genotoxic responses of alkylating agents.Mutation research. Reviews in mutation researchReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent evidence has challenged the default assumption that all DNA-reactive alkylating agents exhibit a linear dose-response. Emerging evidence suggests that the model alkylating agents methyl- and ethylmethanesulfonate and methylnitrosourea (MNU) and ethylnitrosourea observe a nonlinear dose-response with a no observed genotoxic effect level (NOGEL). Follow-up mechanistic studies are essential to understand the mechanism of cellular tolerance and biological relevance of such NOGELs. MNU is one of the most mutagenic simple alkylators. Therefore, understanding the mechanism of mutation induction, following low-dose MNU treatment, sets precedence for weaker mutagenic alkylating agents. Here, we tested MNU at 10-fold lower concentrations than a previous study and report a NOGEL of 0.0075 µg/ml (72.8nM) in human lymphoblastoid cells, quantified through the hypoxanthine (guanine) phosphoribosyltransferase assay (OECD 476). Mechanistic studies reveal that the NOGEL is dependent upon repair of O(6)-methylguanine (O(6)MeG) by the suicide enzyme O(6)MeG-DNA methyltransferase (MGMT). Inactivation of MGMT sensitizes cells to MNU-induced mutagenesis and shifts the NOGEL to the left on the dose axis.
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.