ArticleCarcinogenesis2017
Nickel induces transcriptional down-regulation of DNA repair pathways in tumorigenic and non-tumorigenic lung cells.
Article in Carcinogenesis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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.
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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- The preventive and carcinogenic effect of metals on cancer: a systematic review.BMC public health · 2024Pooled it
- Exclusive Detection of NiJournal of fluorescence · 2025Article
- Article
- Particulate hexavalent chromium inhibits global transcription of genes in DNA repair pathways, particularly targeting homologous recombination repair, base excision repair, mismatch repair and microhomology-mediated end-joining.Journal of hazardous materials · 2025Article
- E-Cigarette effects on oral health: A molecular perspective.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2025Review
- Identification of core carcinogenic elements based on the age-standardized mortality rate of lung cancer in Xuanwei Formation coal in China.Scientific reports · 2024Article
- "Assessing exposure of printing factory workers in thailand to selected heavy metals using urine and hair as non-invasive matrices".BMC public health · 2023Article
- Real-world PMEnvironmental science and pollution research international · 2022Article
- Article
- Molecular Targets of Natural Compounds with Anti-Cancer Properties.International journal of molecular sciences · 2021Review
- Nickel nanoparticle-induced cell transformation: involvement of DNA damage and DNA repair defect through HIF-1α/miR-210/Rad52 pathway.Journal of nanobiotechnology · 2021Article
- Assessing effects of chronic heavy metal exposure through a multibiomarker approach: the case of Liomys irroratus (Rodentia: Heteromyidae).Environmental science and pollution research international · 2021Article
- Nickel carcinogenesis mechanism: cell cycle dysregulation.Environmental science and pollution research international · 2021Review
- Epigenetic influence of environmentally neurotoxic metals.Neurotoxicology · 2020Review
- Update of the risk assessment of nickel in food and drinking water.EFSA journal. European Food Safety Authority · 2020Article
- Impact of hypoxia on DNA repair and genome integrity.Mutagenesis · 2020Review
- Nickel-induced transcriptional changes persist post exposure through epigenetic reprogramming.Epigenetics & chromatin · 2019Article
- Nickel Carcinogenesis Mechanism: DNA Damage.International journal of molecular sciences · 2019Review
- Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair.Nature genetics · 2018Article
- Nickel exposure induces persistent mesenchymal phenotype in human lung epithelial cells through epigenetic activation of ZEB1.Molecular carcinogenesis · 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
5 authors at 1 institution in 1 country.
Funding
Abstract
The heavy metal nickel is a known carcinogen, and occupational exposure to nickel compounds has been implicated in human lung and nasal cancers. Unlike many other environmental carcinogens, however, nickel does not directly induce DNA mutagenesis, and the mechanism of nickel-related carcinogenesis remains incompletely understood. Cellular nickel exposure leads to signaling pathway activation, transcriptional changes and epigenetic remodeling, processes also impacted by hypoxia, which itself promotes tumor growth without causing direct DNA damage. One of the mechanisms by which hypoxia contributes to tumor growth is the generation of genomic instability via down-regulation of high-fidelity DNA repair pathways. Here, we find that nickel exposure similarly leads to down-regulation of DNA repair proteins involved in homology-dependent DNA double-strand break repair (HDR) and mismatch repair (MMR) in tumorigenic and non-tumorigenic human lung cells. Functionally, nickel induces a defect in HDR capacity, as determined by plasmid-based host cell reactivation assays, persistence of ionizing radiation-induced DNA double-strand breaks and cellular hypersensitivity to ionizing radiation. Mechanistically, we find that nickel, in contrast to the metalloid arsenic, acutely induces transcriptional repression of HDR and MMR genes as part of a global transcriptional pattern similar to that seen with hypoxia. Finally, we find that exposure to low-dose nickel reduces the activity of the MLH1 promoter, but only arsenic leads to long-term MLH1 promoter silencing. Together, our data elucidate novel mechanisms of heavy metal carcinogenesis and contribute to our understanding of the influence of the microenvironment on the regulation of DNA repair pathways.
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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.