environmental mutagen
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2022 ◽  
Vol 44 (1) ◽  
Author(s):  
Wan-Qi Chen ◽  
Xin-Yu Zhang

Abstract1,3-Butadiene (BD) is a petrochemical manufactured in high volumes. It is a human carcinogen and can induce lymphohematopoietic cancers, particularly leukemia, in occupationally-exposed workers. BD is an air pollutant with the major environmental sources being automobile exhaust and tobacco smoke. It is one of the major constituents and is considered the most carcinogenic compound in cigarette smoke. The BD concentrations in urban areas usually vary between 0.01 and 3.3 μg/m3 but can be significantly higher in some microenvironments. For BD exposure of the general population, microenvironments, particularly indoor microenvironments, are the primary determinant and environmental tobacco smoke is the main contributor. BD has high cancer risk and has been ranked the second or the third in the environmental pollutants monitored in most urban areas, with the cancer risks exceeding 10-5. Mutagenicity/carcinogenicity of BD is mediated by its genotoxic metabolites but the specific metabolite(s) responsible for the effects in humans have not been determined. BD can be bioactivated to yield three mutagenic epoxide metabolites by cytochrome P450 enzymes, or potentially be biotransformed into a mutagenic chlorohydrin by myeloperoxidase, a peroxidase almost specifically present in neutrophils and monocytes. Several urinary BD biomarkers have been developed, among which N-acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine is the most sensitive and is suitable for biomonitoring BD exposure in the general population. Exposure to BD has been associated with leukemia, cardiovascular disease, and possibly reproductive effects, and may be associated with several cancers, autism, and asthma in children. Collectively, BD is a ubiquitous pollutant that has been associated with a range of adverse health effects and diseases with children being a subpopulation with potentially greater susceptibility. Its adverse effects on human health may have been underestimated and more studies are needed.


2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Satsuki Chikura ◽  
Takafumi Kimoto ◽  
Satoru Itoh ◽  
Hisakazu Sanada ◽  
Shigeharu Muto ◽  
...  

AbstractThe PIGRET assay is one of the Pig-a assays targeting reticulocytes (RETs), an in vivo genotoxicity evaluation method using flow cytometry with endogenous reporter glycosylphosphatidylinositol anchor protein. The PIGRET assay with RETs selectively enriched with anti-CD71 antibodies has several desirable features: high-throughput assay system, low background frequency of mutant cells, and early detection of mutation. To verify the potential and usefulness of the PIGRET assay for short-term testing, an interlaboratory trial involving 16 laboratories organized by the Mammalian Mutagenicity Study Group of the Japanese Environmental Mutagen and Genome Society was conducted. The collaborating laboratories assessed the mutagenicities of a total of 24 chemicals in rats using a single-treatment design and standard protocols for conducting the Pig-a assay on the total red blood cell assay and the PIGRET assay. Here the standard protocol for the PIGRET assay was described in detail.


2020 ◽  
Vol 42 (1) ◽  
Author(s):  
Masamitsu Honma

AbstractThe 6th Asian Congress on Environmental Mutagens (ACEM) was held at Hitotsubashi Hall, Chiyoda City, Tokyo on November 18–20, 2019, in conjunction with the 48th Annual Meeting of the Japanese Environmental Mutagen Society (JEMS). Ninety international delegates from Australia, China, Czechia, France, Germany, India, Iran, Italy, Korea, the Netherlands, the Philippines, the UK, and the USA, along with 340 Japanese delegates and students, participated. During the conference, one keynote lecture, seven symposia, and one workshop were held under the theme of “Innovations towards Environmental Mutagen and Genome Research Originating from Asia.” In the general presentation, 34 oral presentations and 138 poster presentations were made, accompanied by lively discussions. The organizers would like to express their sincere gratitude to those who attended the conference and made it a great success.


2020 ◽  
Vol 42 (1) ◽  
Author(s):  
Robert S. Foster ◽  
Adrian Fowkes ◽  
Alex Cayley ◽  
Andrew Thresher ◽  
Anne-Laure D. Werner ◽  
...  

Abstract The use of in silico predictions for the assessment of bacterial mutagenicity under the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) M7 guideline is recommended when two complementary (quantitative) structure-activity relationship (Q)SAR models are used. Using two systems may increase the sensitivity and accuracy of predictions but also increases the need to review predictions, particularly in situations where results disagree. During the 4th ICH M7/QSAR Workshop held during the Joint Meeting of the 6th Asian Congress on Environmental Mutagens (ACEM) and the 48th Annual Meeting of the Japanese Environmental Mutagen Society (JEMS) 2019, speakers demonstrated their approaches to expert review using 20 compounds provided ahead of the workshop that were expected to yield ambiguous (Q)SAR results. Dr. Chris Barber presented a selection of the reviews carried out using Derek Nexus and Sarah Nexus provided by Lhasa Limited. On review of these compounds, common situations were recognised and are discussed in this paper along with standardised arguments that may be used for such scenarios in future.


2020 ◽  
Vol 40 (20) ◽  
Author(s):  
Shivnarayan Dhuppar ◽  
Sitara Roy ◽  
Aprotim Mazumder

ABSTRACT Ultraviolet (UV) radiation is a major environmental mutagen. Exposure to UV leads to a sharp peak of γH2AX, the phosphorylated form of the histone variant H2AX, in the S phase within an asynchronous population of cells. γH2AX is often considered a definitive marker of DNA damage inside a cell. In this report, we show that γH2AX in the S-phase cells after UV irradiation reports neither on the extent of primary DNA damage in the form of cyclobutane pyrimidine dimers nor on the extent of its secondary manifestations in the form of DNA double-strand breaks or in the inhibition of global transcription. Instead, γH2AX in the S phase corresponds to the sites of active replication at the time of UV irradiation. This accumulation of γH2AX at replication sites slows down the replication. However, the cells do complete the replication of their genomes and arrest within the G2 phase. Our study suggests that it is not DNA damage, but the response elicited, which peaks in the S phase upon UV irradiation.


2019 ◽  
Author(s):  
Shivnarayan Dhuppar ◽  
Sitara Roy ◽  
Aprotim Mazumder

AbstractUltraviolet (UV) radiation is a major environmental mutagen. Exposure to UV leads to a sharp peak of γH2AX – the phosphorylated form of a histone variant H2AX – in the S phase within an asynchronous population of cells. γH2AX is often considered as a definitive marker of DNA damage inside a cell. In this report we show that γH2AX in the S phase cells after UV irradiation does not report on the extent of primary DNA damage in the form of cyclobutane pyrimidine dimers or on the extent of its secondary manifestations as DNA double strand breaks or in the inhibition of global transcription. Instead γH2AX in the S phase corresponds to the sites of active replication at the time of UV irradiation – despite which, the cells complete the replication of their genomes and arrest within the G2 phase. Moreover, cells in all the phases of the cell cycle develop similar levels of DNA damage. Our study suggests that it is not DNA damage but the response elicited, which peaks in the S phase upon UV damage.


2019 ◽  
Vol 41 (1) ◽  
Author(s):  
Katsuyoshi Horibata ◽  
Masashi Sekimoto ◽  
Kei-ichi Sugiyama

Abstract The open symposium of the Japanese Environmental Mutagen Society (JEMS), under the title of “Comprehensive framework between environment and genomic stability,” was held in the Main Conference Room of the Foundation for Promotion of Cancer Research, Tokyo, on June 8, 2019. To understand the relationship between genes and environmental mutagens, the symposium highlights the research activities in the fields of cancer, carcinogenesis and related diseases caused by genomic instabilities, including epigenetic and metabolomic alterations. The symposium was planned to help familiarize attendees with the current trends in research on genome safety. The organizers herein present a summary of the symposium.


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