Environmental and Molecular Mutagenesis最新文献

KCNQ1OT1 has been linked to the development and progression of colorectal cancer (CRC). As a result, functional polymorphisms in the KCNQ1OT1 gene may have a role in CRC formation and progression. The goal of this study was to see if the rs10766212 polymorphism on the KCNQ1OT1 gene was linked to CRC susceptibility and clinical stage in a Chinese Han population. The case–control research comprised a total of 576 CRC patients and 606 healthy controls. The genotype of the rs10766212 polymorphic locus was determined using the Sanger sequencing technique. We found that the KCNQ1OT1 rs10766212 polymorphism was not related to CRC susceptibility; however, it was connected with the clinical stage of CRC. Patients with CRC who had the rs10766212 T allele had a lower risk of stage III/IV tumors than those who had the rs10766212 C allele. Furthermore, CRC tissues with the rs10766212 CC genotype showed a significant negative connection between KCNQ1OT1 and hsa-miR-622 expression. The luciferase assay showed that the rs10766212 C allele might contribute to the adsorption of KCNQ1OT1 on hsa-miR-622. In conclusion, the rs10766212 polymorphism altering hsa-miR-622 binding is linked to the clinical stage of CRC and may serve as a biomarker for predicting CRC progression in the Chinese Han population. However, better-designed studies are still needed to confirm the current findings.

Over 70,000 DNA lesions occur in the cell every day, and the inability to properly repair them can lead to mutations and destabilize the genome, resulting in carcinogenesis. The base excision repair (BER) pathway is critical for maintaining genomic integrity by repairing small base lesions, abasic sites and single-stranded breaks. Monofunctional and bifunctional glycosylases initiate the first step of BER by recognizing and excising specific base lesions, followed by DNA end processing, gap filling, and finally nick sealing. The Nei-like 2 (NEIL2) enzyme is a critical bifunctional DNA glycosylase in BER that preferentially excises cytosine oxidation products and abasic sites from single-stranded, double-stranded, and bubble-structured DNA. NEIL2 has been implicated to have important roles in several cellular functions, including genome maintenance, participation in active demethylation, and modulation of the immune response. Several germline and somatic variants of NEIL2 with altered expression and enzymatic activity have been reported in the literature linking them to cancers. In this review, we provide an overview of NEIL2 cellular functions and summarize current findings on NEIL2 variants and their relationship to cancer.

Dietary exposure to aflatoxin B₁ (AFB₁) is a recognized risk factor for developing hepatocellular carcinoma. The mutational signature of AFB₁ is characterized by high-frequency base substitutions, predominantly G>T transversions, in a limited subset of trinucleotide sequences. The 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxyaflatoxin B₁ (AFB₁-FapyGua) has been implicated as the primary DNA lesion responsible for AFB₁-induced mutations. This study evaluated the mutagenic potential of AFB₁-FapyGua in four sequence contexts, including hot- and cold-spot sequences as apparent in the mutational signature. Vectors containing site-specific AFB₁-FapyGua lesions were replicated in primate cells and the products of replication were isolated and sequenced. Consistent with the role of AFB₁-FapyGua in AFB₁-induced mutagenesis, AFB₁-FapyGua was highly mutagenic in all four sequence contexts, causing G>T transversions and other base substitutions at frequencies of ~80%–90%. These data suggest that the unique mutational signature of AFB₁ is not explained by sequence-dependent fidelity of replication past AFB₁-FapyGua lesions.

The comet assay is a sensitive method for the evaluation of DNA damages and DNA repair capacity at single-cell level. Allium cepa is a well-established plant model for toxicological studies. The aim of this scoping review was to investigate the recent application of the comet assay in Allium cepa root cells to assess the genotoxicity. To explore the literature a search was performed selecting articles published between January 2015 and February 2023 from Web of Science, PubMed, and Scopus databases using the combined search terms “Comet assay” and “Allium cepa”. All the original articles that applied the comet assay to Allium cepa root cells were included. Of the 334 records initially found, 79 articles were identified as meeting the inclusion criteria. Some studies reported results for two or more toxicants. In these cases, the data for each toxicant were treated separately. Thus, the number of analyzed toxicants (such as chemicals, new materials, and environmental matrices) was higher than the number of selected papers and reached 90. The current use of the Allium-comet assay seems to be directed towards two types of approach: the direct study of the genotoxicity of compounds, mainly biocides (20% of analyzed compounds) and nano- and microparticles (17%), and assessing a treatment's ability to reduce or eliminate genotoxicity of known genotoxicants (19%). Although the genotoxicity identified by the Allium-comet assay is only one piece of a larger puzzle, this method could be considered a useful tool for screening the genotoxic potential of compounds released into the environment.

The melanogenesis pathway regulates pigmentation through the synergic action of various genes. We are interested in analyzing the genetic variations in the ASIP which determine eumelanin production in the dermis layer. In the present study, the ASIP gene was characterized in buffalo and 268 genetically unrelated buffaloes belonging to 10 different populations were genotyped for the non-synonymous SNP (c.292C>T) identified in the exon 3 region of the gene using Tetra-ARMS-PCR. The TT genotype occurred at a higher rate in Murrah, followed by Nili Ravi, Tripura, and Paralakhemundi (42.63%, 19.30%, 3.45%, and 3.33%). These results convey the association of the black coat color of Murrah with the ASIP gene TT genotype and the lighter shades of black coat (brown and grayish-black) color phenotype in other breeds with the CC genotype.

Kuchi Bhotla, H., Balasubramanian, B., Rengasamy, K.R.R., Arumugam, V.A., Alagamuthu, K.K., Chithravel, V. et al. (2023) Genotoxic repercussion of high-intensity radiation (x-rays) on hospital radiographers. Environmental and Molecular Mutagenesis, 64(2), 123–131.

In the original article the Ethics approval section has not been included. The Ethics approval section should read as follows:

ETHICS APPROVAL STATEMENT

The study was approved and got its ethical clearance from the Institutional committee from Christ University (Ethical Reference No. ECR/793/Inst/KA/2015/RR-18) and followed the protocols of ethical standards of Declaration of Helsinki 1964, WMA, 2000.

We apologize for this error.

Amygdalin (AMY), a plant secondary metabolite containing nitrile, is a major component of the seeds of Rosaceae family plants. It is known that this compound has many pharmacological activities such as cancer prevention, antipyretic, and cough suppressant. In this study, the genotoxic and modulatory effects of amygdalin were assessed by chromosomal aberration (CA), sister chromatid exchange (SCE), and cytokinesis-block micronucleus assay (CBMN) assays using human peripheral lymphocytes (HPLs) in the absence and presence of metabolic activator (S9 mix). Lymphocytes were exposed to various concentrations of amygdalin (0.86, 1.72, 3.43, 6.86, and 13.75 μg/mL) alone and in combination with mitomycin-C (MMC, 0.20 μg/mL) or cyclophosphamide (CP, 12 μg/mL). The mitotic index (MI), replication index (RI), cytokinesis-block proliferation index (CBPI), and cytostasis were also evaluated to determine cytotoxicity. Amygdalin alone did not exhibit genotoxic and cytotoxic effects at all the tested concentrations both in the absence and presence of the S9 mix. In contrast, amygdalin significantly reduced the frequencies of CA (especially at 48 h treatments), SCE, and MN (except 0.86 μg/mL in pre- and simultaneous treatment) induced by MMC in all the tested concentrations and treatment protocols. It has also considerably decreased CP-induced CA and SCE frequencies at all the concentrations (except 0.86 μg/mL) in simultaneous treatment. This study demonstrated that amygdalin alone was not genotoxic, on the contrary, it has revealed modulatory effects against chemotherapy agents that induced genomic damage in human lymphocytes, suggesting its chemopreventive potential.

Historical negative control data (HCD) have played an increasingly important role in interpreting the results of genotoxicity tests. In particular, Organisation for Economic Co-operation and Development (OECD) genetic toxicology test guidelines recommend comparing responses produced by exposure to test substances with the distribution of HCD as one of three criteria for evaluating and interpreting study results (referred to herein as "Criterion C"). Because of the potential for inconsistency in how HCD are acquired, maintained, described, and used to interpret genotoxicity testing results, a workgroup of the International Workshops for Genotoxicity Testing was convened to provide recommendations on this crucial topic. The workgroup used example data sets from four in vivo tests, the Pig-a gene mutation assay, the erythrocyte-based micronucleus test, the transgenic rodent gene mutation assay, and the in vivo alkaline comet assay to illustrate how the quality of HCD can be evaluated. In addition, recommendations are offered on appropriate methods for evaluating HCD distributions. Recommendations of the workgroup are: When concurrent negative control data fulfill study acceptability criteria, they represent the most important comparator for judging whether a particular test substance induced a genotoxic effect. HCD can provide useful context for interpreting study results, but this requires supporting evidence that (i) HCD were generated appropriately, and (ii) their quality has been assessed and deemed sufficiently high for this purpose. HCD should be visualized before any study comparisons take place; graph(s) that show the degree to which HCD are stable over time are particularly useful. Qualitative and semi-quantitative assessments of HCD should also be supplemented with quantitative evaluations. Key factors in the assessment of HCD include: (i) the stability of HCD over time, and (ii) the degree to which inter-study variation explains the total variability observed. When animal-to-animal variation is the predominant source of variability, the relationship between responses in the study and an HCD-derived interval or upper bounds value (i.e., OECD Criterion C) can be used with a strong degree of confidence in contextualizing a particular study's results. When inter-study variation is the major source of variability, comparisons between study data and the HCD bounds are less useful, and consequentially, less emphasis should be placed on using HCD to contextualize a particular study's results. The workgroup findings add additional support for the use of HCD for data interpretation; but relative to most current OECD test guidelines, we recommend a more flexible application that takes into consideration HCD quality. The workgroup considered only commonly used in vivo tests, but it anticipates that the same principles will apply to other genotoxicity tests, including many in vitro tests.

Male B6C3F1 mice were administered styrene monomer by oral gavage for 29 consecutive days at dose levels of 0, 75, 150, or 300 mg/kg/day. The highest dose level represented the maximum tolerated dose based on findings in a 28-day dose range-finding study, in which the bioavailability of orally administered styrene was also confirmed. The positive control group received ethyl nitrosourea (ENU; 51.7 mg/kg/day) on Study Days 1–3 and ethyl methanesulfonate (EMS; 150 mg/kg/day) on Study Days 27–29 by oral gavage. Approximately 3 h following the final dose, blood was collected to assess erythrocyte Pig-a mutant and micronucleus frequencies. DNA strand breakage was assessed in glandular stomach, duodenum, kidney, liver, and lung tissues using the alkaline comet assay. The %tail DNA for stomach, liver, lung, and kidney in the comet assay among the styrene-treated groups was neither significantly different from the respective vehicle controls nor was there any dose-related increasing trend in any of the tissues; results for duodenum were interpreted to be inconclusive because of technical issues. The Pig-a and micronucleus frequencies among styrene-treated groups also did not show significant increases relative to the vehicle controls and there was also no evidence for a dose-related increasing trend. Thus, orally administered styrene did not induce DNA damage, mutagenesis, or clastogenesis/aneugenesis in these Organization of Economic Co-operation and Development test guideline-compliant genotoxicity studies. Data from these studies can contribute to the overall assessment of genotoxic hazard and risk posed to humans potentially exposed to styrene.

This study assessed, for the first time, the expression of the genes hOGG1, TP53, and IL-6 in leukocytes by real-time quantitative polymerase chain reaction in surgical patients before (baseline), during (2 h of anesthesia) and 1 day after sevoflurane anesthesia. Additionally, DNA damage was detected by the comet assay, serum interleukin (IL)-6 was detected by flow cytometry, and differential leukocyte counting was also performed. TP53 and hOGG1 expression was downregulated on the day after anesthesia compared to before anesthesia. However, IL-6 expression did not change, and no DNA damage induction was observed during or after anesthesia. At the systemic level, mild neutrophilia and an increase in IL-6 levels occurred after anesthesia. Our findings suggest that sevoflurane anesthesia downregulates gene expression (hOGG1 and TP53) and contributes to an inflammatory status (increased systemic IL-6 and mild neutrophilia) but is not associated with DNA damage in patients without comorbidities who undergo minor elective surgery.