Stefana Vuletić , Marina Bekić , Sergej Tomić , Biljana Nikolić , Stefana Cvetković , Tea Ganić , Dragana Mitić-Ćulafić
{"title":"Could alder buckthorn (Frangula alnus Mill) be a source of chemotherapeutics effective against hepato- and colorectal carcinoma? An in vitro study","authors":"Stefana Vuletić , Marina Bekić , Sergej Tomić , Biljana Nikolić , Stefana Cvetković , Tea Ganić , Dragana Mitić-Ćulafić","doi":"10.1016/j.mrgentox.2023.503706","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2023.503706","url":null,"abstract":"<div><p>Among numerous types of cancer, hepatocellular and colorectal carcinoma are important causes of mortality. Given the nature of these cancer types and their resistance, it is of great importance to find new chemotherapeutics and therapy targets, so plant products seem to be an excellent choice in such search. The main goal of this study was to investigate anticancer activity of <em>Frangula alnus</em> ethyl-acetate extract (FA) and its dominant constituent emodin (E) on hepatocellular and colorectal carcinoma cell lines, HepG2 and HCT116, as well as on normal MRC-5 fibroblasts. Cytotoxicity was investigated in MTT test and both FA and E showed strong reduction of cell viability in cancer cells. Flow cytometer analysis demonstrated that FA and E led to G1 phase arrest and slight accumulation of cells in the G2/M phase; additionally, annexinV-FITC/7AAD dying showed that FA and E decreased cell viability and triggered apoptosis in all cell lines. FA and E evidenced strong genotoxic potential in comet assay performed on all cell lines, while tests measuring antioxidative potential (DPPH and TBA) demonstrated strong effect of FA. It could be concluded that both FA and E have significant anticancer activity against hepatocellular and colorectal carcinoma cell lines HepG2 and HCT116, but notable selectivity was not observed.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"892 ","pages":"Article 503706"},"PeriodicalIF":1.9,"publicationDate":"2023-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49849069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammad Alzaben , Regina Burve , Katrin Loeschner , Peter Møller , Martin Roursgaard
{"title":"Nanoplastics from ground polyethylene terephthalate food containers: Genotoxicity in human lung epithelial A549 cells","authors":"Mohammad Alzaben , Regina Burve , Katrin Loeschner , Peter Møller , Martin Roursgaard","doi":"10.1016/j.mrgentox.2023.503705","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2023.503705","url":null,"abstract":"<div><p>The ubiquitous pollution of plastic particles in most environmental matrices leads to concern about any potential adverse effects on human health. Most studies on the toxicological effect of nanoplastics has focused on standard particles of polystyrene. In reality humans are exposed to a large variety of different types and sizes of plastic material via oral intake and inhalation. In this study, we investigated the effect of polyethylene terephthalate (PET) nanoplastic particles from ground food containers from a supermarket. The aim was to investigate a possible link between exposure to PET nanoplastics and genotoxic response in a cell model of the human airway epithelial (A549) cells. Further, we investigated the combined effect of PET and chemicals known to alter the cellular redox state, as a model of partially compromised antioxidant defense system. DNA damage was assessed by the alkaline comet assay. The ground PET nanoplastics have a mean hydrodynamic diameter of 136 nm in water. The results showed that PET exposure led to increased reactive oxygen species production (approximately 30 % increase compared to unexposed cells). In addition, exposure to PET nanoplastic increased the level of DNA strand breaks (net increase = 0.10 lesions/10<sup>6</sup> base pair, 95 % confidence interval: 0.01, 0.18 lesions/10<sup>6</sup> base pair). Pre- or post-exposure to hydrogen peroxide or buthionine sulfoximine did not lead to a higher level of DNA damage. Overall, the study shows that exposure to PET nanoplastics increases both intracellular reactive oxygen production and DNA damage in A549 cells.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"892 ","pages":"Article 503705"},"PeriodicalIF":1.9,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49849070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mariana de Oliveira Klein , Luiza Flavia Veiga Francisco , Izabela Natália Faria Gomes , Sergio V. Serrano , Rui M. Reis , Henrique C.S. Silveira
{"title":"Hazard assessment of antineoplastic drugs and metabolites using cytotoxicity and genotoxicity assays","authors":"Mariana de Oliveira Klein , Luiza Flavia Veiga Francisco , Izabela Natália Faria Gomes , Sergio V. Serrano , Rui M. Reis , Henrique C.S. Silveira","doi":"10.1016/j.mrgentox.2023.503704","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2023.503704","url":null,"abstract":"<div><p>Antineoplastic drugs are among the most toxic pharmaceuticals. Their release into the aquatic ecosystems has been reported, giving rise to concerns about the adverse effects, including cytotoxicity and genotoxicity, that they may have on exposed organisms. In this study, we analyzed the cytotoxicity and genotoxicity of 5-fluorouracil (5-FU) and its metabolite alpha-fluoro-beta-alanine (3-NH2-F); gemcitabine (GEM) and its metabolite 2′-deoxy-2′,2′-difluorouridine (2-DOH-DiF); as well as cyclophosphamide (CP) on the HepG2 cell line. Drug concentrations were based on those previously observed in the effluent of a major cancer hospital in Brazil. The study found that GEM, 2-DOH-DiF and 5-FU resulted in reduced cell viability. No reduction in cell viability was observed for CP and 3-NH2-F. Genotoxic assessment revealed damage in the form of nucleoplasmic bridges for CP and 3-NH2-F. The tested concentrations of all compounds resulted in significantly increased MNi and NBUDs. The results showed that these compounds induced cytotoxic and genotoxic effects in HepG2 cells at concentrations found in the environment. To the best of our knowledge, this study is the first to report on the cytogenotoxic impacts of the metabolites 3-NH2-F and 2-DOH-DiF in HepG2 cells. These findings may help in the development of public policies that could minimize potential environmental contamination.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"892 ","pages":"Article 503704"},"PeriodicalIF":1.9,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49849064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joel P. Bercu , Shaofei Zhang , Zhanna Sobol , Patricia A. Escobar , Phu Van , Maik Schuler
{"title":"Comparison of the transgenic rodent mutation assay, error corrected next generation duplex sequencing, and the alkaline comet assay to detect dose-related mutations following exposure to N-nitrosodiethylamine","authors":"Joel P. Bercu , Shaofei Zhang , Zhanna Sobol , Patricia A. Escobar , Phu Van , Maik Schuler","doi":"10.1016/j.mrgentox.2023.503685","DOIUrl":"10.1016/j.mrgentox.2023.503685","url":null,"abstract":"<div><p><em>N</em>-Nitrosodiethylamine (NDEA), a well-studied <em>N</em>-nitrosamine, was tested in rats to compare the dose-response relationship of three genotoxicity endpoints. Mutant / mutation frequencies were determined using the transgenic rodent (TGR) gene mutation assay and error corrected next generation sequencing (ecNGS) (i.e., duplex sequencing (DS)), and genetic damage was detected by the alkaline comet assay. Big Blue® <em>(cII</em> Locus) animals (n = 6 per dose group) were administered doses of 0.001, 0.01, 0.1, 1, 3 mg/kg/day NDEA by oral gavage. Samples were collected for <em>cII</em> mutation and DS analyses following 28-days of exposure and 3 days recovery. In a separate study, male Sprague-Dawley (SD) rats (n = 6 per dose group) were administered the same doses by oral gavage for two consecutive days and then samples collected for the alkaline comet assay. A dose-related increase in mutant / mutation frequencies of the liver but not duodenum was observed using the TGR assay and DS with DS resulting in a slightly more sensitive response, with a lower benchmark dose (BMD). In addition, a dose-related increase in percent tail DNA was observed in the liver using the alkaline comet assay. Therefore, DS and comet assays showed good utility for hazard identification and dose-response analysis of a representative <em>N</em>-nitrosamine comparable to the TGR gene mutation assay.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"891 ","pages":"Article 503685"},"PeriodicalIF":1.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41132165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Erik Bivehed , Björn Hellman , Yuting Fan , Jakob Haglöf , Sonja Buratovic
{"title":"DNA integrity under alkaline conditions: An investigation of factors affecting the comet assay","authors":"Erik Bivehed , Björn Hellman , Yuting Fan , Jakob Haglöf , Sonja Buratovic","doi":"10.1016/j.mrgentox.2023.503680","DOIUrl":"10.1016/j.mrgentox.2023.503680","url":null,"abstract":"<div><p>The effect of pH on DNA integrity was assessed using a three-step approach. The comet assay was used on a whole genome level, with three different protocols: neutral (no alkaline unwinding), flash (pH 12.5 with 2.5 min unwinding), and the conventional alkaline protocol (pH>13 with 40 min unwinding). Real-time quantitative PCR (RT-qPCR) was then used to study the isolated DNA, revealing that gene amplification decreased with increasing pH, indicating DNA degradation. Specially designed molecular beacons were used to examine DNA at the molecular level, with or without alkali-labile site (ALS) insertions. At pH 12.5, fluorescence in the hairpins with ALS started to increase after 30 min, while at pH> 13, this increase was already observed after 5 min, indicating a significant increase in DNA strand breaks. Liquid chromatography analysis was also used, demonstrating that the hairpins remained intact up to pH 10, even after 1 h exposure, whereas, at pH 12.5, partial conversion into strand breaks occurred after 30 min. At pH> 13, the hairpins were almost completely degraded after 30 min. The flash protocol effectively detects DNA single- and double-strand breaks and identified these damages after 2.5 min of alkaline treatment at pH 12.5. When the hairpins were exposed to pH 12.5 for 60 min, ALS were converted to strand breaks, demonstrating the sensitivity of this approach to detect changes in DNA structure. These findings indicate that pH poses a substantial risk to DNA integrity, leading to significantly higher background levels of DNA damage compared to conditions closer to neutrality. Our study demonstrates the importance of understanding the influence of pH on DNA stability and provides insights into risks associated with alkaline environments, especially at pH> 13.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"891 ","pages":"Article 503680"},"PeriodicalIF":1.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41136077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Milagros R.R. Laborde , Marcelo L. Larramendy , Sonia Soloneski
{"title":"Cytotoxic and genotoxic profiles of the pyrethroid insecticide lambda-cyhalothrin and its microformulation Karate® in CHO-K1 cells","authors":"Milagros R.R. Laborde , Marcelo L. Larramendy , Sonia Soloneski","doi":"10.1016/j.mrgentox.2023.503682","DOIUrl":"10.1016/j.mrgentox.2023.503682","url":null,"abstract":"<div><p>Lambda-cyhalothrin (LCT) and its microformulation Karate® (25 % a.i.) were analysed for its genotoxicity and cytotoxicity on Chinese hamster ovary (CHO-K1) cells. Cytokinesis-block micronucleus cytome (CBMN-cyt) and alkaline single-cell gel electrophoresis (SCGE) bioassays were selected to test genotoxicity. Neutral red uptake (NRU), succinic dehydrogenase activity (MTT) and apoptogenic induction were employed for estimating cytotoxicity. Both compounds were analysed within a concentration range of 0.1–100 µg/mL. Only LCT produced a significant augment in the frequency of micronuclei (MNs) when the cultures were exposed to highest concentrations of 10 and 100 µg LCT/mL. A noticeable decrease in NDI was observed for cultures treated with LCT at 10 and 100 µg/mL. Karate® induced the inhibition of both the proportion of viable cells and succinic dehydrogenase activity and triggered apoptosis 24 h of exposition. Whilst an increased GDI in CHO-K1 cells was observed in the treatments with 1–100 µg Karate®/mL, the GDI was not modified in the treatments employing LCT at equivalent doses. SCGE showed that Karate® was more prone to induce genotoxic effects than LCT. Only 50 µg/mL of Karate® was able to increase apoptosis. Our results demonstrate the genomic instability and cytotoxic effects induced by this pyrethroid insecticide, confirming that LCT exposure can result in a severe drawback for the ecological equilibrium of the environment.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"891 ","pages":"Article 503682"},"PeriodicalIF":1.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41100986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Blood molecular profile to predict genotoxicity from exposure to antineoplastic drugs","authors":"Carina Ladeira , Rúben Araújo , Luís Ramalhete , Hélder Teixeira , Cecília R.C. Calado","doi":"10.1016/j.mrgentox.2023.503681","DOIUrl":"10.1016/j.mrgentox.2023.503681","url":null,"abstract":"<div><p>Genotoxicity is an important information that should be included in human biomonitoring programmes. However, the usually applied cytogenetic assays are laborious and time-consuming, reason why it is critical to develop rapid and economic new methods. The aim of this study was to evaluate if the molecular profile of frozen whole blood, acquired by Fourier Transform Infrared (FTIR) spectroscopy, allows to assess genotoxicity in occupational exposure to antineoplastic drugs, as obtained by the cytokinesis-block micronucleus assay. For that purpose, 92 samples of peripheral blood were studied: 46 samples from hospital professionals occupationally exposed to antineoplastic drugs and 46 samples from workers in academia without exposure (controls). It was first evaluated the metabolome from frozen whole blood by methanol precipitation of macromolecules as haemoglobin, followed by centrifugation. The metabolome molecular profile resulted in 3 ratios of spectral bands, significantly different between the exposed and non-exposed group (p < 0.01) and a spectral principal component-linear discriminant analysis (PCA-LDA) model enabling to predict genotoxicity from exposure with 73 % accuracy. After optimization of the dilution degree and solution used, it was possible to obtain a higher number of significant ratios of spectral bands, <em>i.e.</em>, 10 ratios significantly different (p < 0.001), highlighting the high sensitivity and specificity of the method. Indeed, the PCA-LDA model, based on the molecular profile of whole blood, enabled to predict genotoxicity from the exposure with an accuracy, sensitivity, and specificity of 92 %, 93 % and 91 %, respectively. All these parameters were achieved based on 1 μL of frozen whole blood, in a high-throughput mode, <em>i.e.</em>, based on the simultaneous analysis of 92 samples, in a simple and economic mode. In summary, it can be conclude that this method presents a very promising potential for high-dimension screening of exposure to genotoxic substances.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"891 ","pages":"Article 503681"},"PeriodicalIF":1.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41134857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrey A. Toropov, Alla P. Toropova, Alessandra Roncaglioni, Emilio Benfenati
{"title":"In silico prediction of the mutagenicity of nitroaromatic compounds using correlation weights of fragments of local symmetry","authors":"Andrey A. Toropov, Alla P. Toropova, Alessandra Roncaglioni, Emilio Benfenati","doi":"10.1016/j.mrgentox.2023.503684","DOIUrl":"10.1016/j.mrgentox.2023.503684","url":null,"abstract":"<div><p>Most quantitative structure-property/activity relationships (QSPRs/QSARs) techniques involve using different programs separately for generating molecular descriptors and separately for building models based on available descriptors. Here, the capabilities of the CORAL program are evaluated. A user of the program should apply as the basis for models the representation of the molecular structure by means of the simplified molecular input-line entry system (SMILES) as well as experimental data on the endpoint of interest. The local symmetry of SMILES is a novel composition of symmetrically represented symbols, which are three ‘<em>xyx</em>’, four ‘<em>xyyx</em>’, or five symbols ‘<em>xyzyx</em>’. We updated our CORAL software using this optimal, new flexible descriptor, sensitive to the symmetric composition of a specific part of the molecule. Computational experiments have shown that taking account of these attributes of SMILES can improve the predictive potential of models for the mutagenicity of nitroaromatic compounds. In addition, the above computational experiments have confirmed the advantage of using the index of ideality of correlation (<em>IIC</em>) and the correlation intensity index (<em>CII</em>) for Monte Carlo optimization of the correlation weights for various attributes of SMILES, including the local symmetry. The average value of the coefficient of determination for the validation set (five different models) without fragments of local symmetry is 0.8589 ± 0.025, whereas using fragments of local symmetry improves this criterion of the predictive potential up to 0.9055 ± 0.010.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"891 ","pages":"Article 503684"},"PeriodicalIF":1.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41134932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vasily N. Dobrovolsky , Tomonari Matsuda , Page McKinzie , Jaime Miranda , Javier R. Revollo
{"title":"Whole-genome high-fidelity sequencing: A novel approach to detecting and characterization of mutagenicity in vivo","authors":"Vasily N. Dobrovolsky , Tomonari Matsuda , Page McKinzie , Jaime Miranda , Javier R. Revollo","doi":"10.1016/j.mrgentox.2023.503691","DOIUrl":"10.1016/j.mrgentox.2023.503691","url":null,"abstract":"<div><p>Direct DNA sequencing can be used for characterizing mutagenicity in simple and complex biological models. Recently we described a method of whole-genome sequencing for detecting mutations in simple models of cultured bacteria, mammalian cells, and nematode. In the current proof-of-concept study, we expand and improve our method for evaluating a more complex mammalian biological model in outbred mice. We detail the method by applying it to a small set of animals treated with a mutagen with known mutagenicity profiles, <em>N</em>-ethyl-<em>N</em>-nitrosourea (ENU), for consistency with the known data. Whole-genome high-fidelity sequencing (HiFi Sequencing) showed frequencies and spectra of background mutations in tissues of untreated mice that were consistent with normal ageing and characterized by spontaneous or enzymatic deamination of 5-methylcytosine. In mice treated with a single 40 mg/kg dose of ENU, the frequency of mutations in the genomic DNA of solid tissues increased up to 7-fold, with the greatest increase observed in the spleen and the smallest increase in the liver. The most common mutations detected in ENU-treated mice were T > A transitions and T > C transversions, consistent with the types of mutations caused by alkylating agents. The data suggest that HiFi Sequencing may be useful for characterizing mutagenicity of novel compounds in various biological models.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"891 ","pages":"Article 503691"},"PeriodicalIF":1.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41155655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation and interpretation of cytogenetic test results based on biological relevance","authors":"Makoto Hayashi","doi":"10.1016/j.mrgentox.2023.503693","DOIUrl":"10.1016/j.mrgentox.2023.503693","url":null,"abstract":"<div><p>The evaluation and interpretation of cytogenetic test data are discussed from the perspective of biological relevance. The reliability of tests must be considered, before evaluation and interpretation. Statistical procedures are important for the evaluation of test data, but for human health risk assessment, biological relevance is essential. Cell culture conditions must be carefully considered. Cells must be healthy in the physiologically controlled culture medium. Osmolality, pH, and temperature are critical factors in keeping the culture medium physiologically normal and avoiding artifactual responses. Careful attention must be paid to the exposure of test chemicals to target cells, in both <em>in vitro</em> and <em>in vivo</em> tests. For <em>in vivo</em> tests, absorption, distribution, metabolism, and excretion are critical issues that affect the exposure of the target cells to the test chemical. The dose-response relationship and reproducibility are also critical factors in biological reliability. I also discuss why so many chemicals show positive results in <em>in vitro</em> cytogenetic assays.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"891 ","pages":"Article 503693"},"PeriodicalIF":1.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41127085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}