ArticleGenes and environment : the official journal of the Japanese Environmental Mutagen Society2015
An in vitro method for detecting genetic toxicity based on inhibition of RNA synthesis by DNA lesions.
Article in Genes and environment : the official journal of the Japanese Environmental Mutagen Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- Effects of acetaldehyde-induced DNA lesions on DNA metabolism.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2020Article
- Discovery of a novel DNA polymerase inhibitor and characterization of its antiproliferative properties.Cancer biology & therapy · 2019Article
- Aging and neurodegeneration are associated with increased mutations in single human neurons.Science (New York, N.Y.) · 2018Article
- Article
- Interaction Analysis of T7 RNA Polymerase with Heparin and Its Low Molecular Weight Derivatives - An In Silico Approach.Bioinformatics and biology insights · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionA wide variety of DNA lesions such as ultraviolet light-induced photoproducts and chemically induced bulky adducts and crosslinks (intrastrand and interstrand) interfere with replication and lead to mutations and cell death. In the human body, these damages may cause cancer, inborn diseases, and aging. So far, mutation-related actions of DNA polymerases during replication have been intensively studied. However, DNA lesions also block RNA synthesis, making the detection of their effects on transcription equally important for chemical safety assessment. Previously, we established an in vivo method for detecting DNA damage induced by ultraviolet light and/or chemicals via inhibition of RNA polymerase by visualizing transcription.
resultsHere, we present an in vitro method for detecting the effects of chemically induced DNA lesions using in vitro transcription with T7 RNA polymerase and real-time reverse transcription polymerase chain reaction (PCR) based on inhibition of in vitro RNA synthesis. Conventional PCR and real-time reverse transcription PCR without in vitro transcription can detect DNA lesions such as complicated cisplatin DNA adducts but not UV-induced lesions. We found that only this combination of in vitro transcription and real-time reverse transcription PCR can detect both cisplatin- and UV-induced DNA lesions that interfere with transcription.
conclusionsWe anticipate that this method will be useful for estimating the potential transcriptional toxicity of chemicals in terminally differentiated cells engaged in active transcription and translation but not in replication.
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