Mutagenesis最新文献_第10页

UCTD and SLE patients show increased levels of oxidative and DNA damage together with an altered kinetics of DSB repair. UCTD和SLE患者表现出氧化和DNA损伤水平增加，同时DSB修复动力学改变。

IF 2.7 4区医学

Mutagenesis Pub Date : 2021-11-29 DOI: 10.1093/mutage/geab036

Consuelo Micheli, Alice Parma, Chiara Tani, Domenica Di Bello, Aurora Falaschi, Anna Chiaramonte, Serena Testi, Marta Mosca, Roberto Scarpato

{"title":"UCTD and SLE patients show increased levels of oxidative and DNA damage together with an altered kinetics of DSB repair.","authors":"Consuelo Micheli, Alice Parma, Chiara Tani, Domenica Di Bello, Aurora Falaschi, Anna Chiaramonte, Serena Testi, Marta Mosca, Roberto Scarpato","doi":"10.1093/mutage/geab036","DOIUrl":"https://doi.org/10.1093/mutage/geab036","url":null,"abstract":"Immunological tolerance is a critical feature of the immune system; its loss might lead to an abnormal response of lymphocytes causing autoimmune diseases. One of the most important groups belonging to autoimmune disorders is the connective tissue diseases (CTD). CTD are classified among systemic rheumatic diseases and include pathologies such as systemic lupus erythematosus (SLE), and undifferentiated CTD (UCTD). In this study, we evaluated oxidative and genome damage in peripheral blood lymphocytes from patients with SLE and UCTD, further classified on the basis of disease activity and the presence/absence of a serological profile. Oxidative damage was evaluated in cell membrane using the fluorescent fatty acid analogue BODIPY 581/591 C11. The percentage of oxidised lymphocytes in both SLE and UCTD patients was higher than in the control group, and the oxidative stress correlated positively with both disease activity and autoantibody profile. The γH2AX focus assay was used to quantify the presence of spontaneous double strand breaks (DSBs), and to assess the abilities of DSBs repair system after T cells were treated with mitomycin C (MMC). Subjects with these autoimmune disorders showed a higher number of γH2AX foci than healthy controls, but no correlation with diseases activity and presence of serological profile was observed. In addition, patients displayed an altered response to MMC-induced DSBs, which led their peripheral cells to greatly increase apoptosis. Taken together our results confirmed an interplay among oxidative stress, DNA damage and impaired DNA repair, which are directly correlated to the aggressiveness and clinical progression of the diseases. We propose the evaluation of these molecular markers to better characterize SLE and UCTD, aiming to improve the treatment plan and the quality of the patients' life.","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"36 6","pages":"429-436"},"PeriodicalIF":2.7,"publicationDate":"2021-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39445586","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}

引用次数: 2

In vitro and integrated in vivo strategies to reduce animal use in genotoxicity testing. 体外和体内综合策略，以减少遗传毒性试验中动物的使用。

IF 2.7 4区医学

Mutagenesis Pub Date : 2021-11-29 DOI: 10.1093/mutage/geab035

Katherine Groff, Stephen J Evans, Shareen H Doak, Stefan Pfuhler, Raffaella Corvi, Samantha Saunders, Gilly Stoddart

{"title":"In vitro and integrated in vivo strategies to reduce animal use in genotoxicity testing.","authors":"Katherine Groff, Stephen J Evans, Shareen H Doak, Stefan Pfuhler, Raffaella Corvi, Samantha Saunders, Gilly Stoddart","doi":"10.1093/mutage/geab035","DOIUrl":"https://doi.org/10.1093/mutage/geab035","url":null,"abstract":"Scientific, financial, and ethical drivers have led to unprecedented interest in implementing human-relevant, mechanistic in vitro and in silico testing approaches. Further, as non-animal approaches are being developed and validated, researchers are interested in strategies that can immediately reduce the use of animals in toxicology testing. Here, we aim to outline a testing strategy for assessing genotoxicity beginning with standard in vitro methods, such as the bacterial reverse mutation test and the in vitro micronucleus test, followed by a second tier of in vitro assays including those using advanced 3D tissue models. Where regulatory agencies require in vivo testing, one demonstrated strategy is to combine genotoxicity studies traditionally conducted separately into a single test or to integrate genotoxicity studies into other toxicity studies. Standard setting organisations and regulatory agencies have encouraged such strategies, and examples of their use can be found in the scientific literature. Employing approaches outlined here will reduce animal use as well as study time and costs.","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"36 6","pages":"389-400"},"PeriodicalIF":2.7,"publicationDate":"2021-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39442062","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}

引用次数: 4

Genotoxicity of advanced glycation end products in vitro is influenced by their preparation temperature, purification and cell exposure time. 晚期糖基化终产物的体外遗传毒性受其制备温度、纯化和细胞暴露时间的影响。

IF 2.7 4区医学

Mutagenesis Pub Date : 2021-11-29 DOI: 10.1093/mutage/geab037

Emma L Jaunay, Varinderpal S Dhillon, Susan J Semple, Bradley S Simpson, Maulik Ghetia, Permal Deo, Michael Fenech

{"title":"Genotoxicity of advanced glycation end products in vitro is influenced by their preparation temperature, purification and cell exposure time.","authors":"Emma L Jaunay, Varinderpal S Dhillon, Susan J Semple, Bradley S Simpson, Maulik Ghetia, Permal Deo, Michael Fenech","doi":"10.1093/mutage/geab037","DOIUrl":"https://doi.org/10.1093/mutage/geab037","url":null,"abstract":"Advanced glycation end products (AGEs) are formed via non-enzymatic reactions between amino groups of proteins and the carbonyl groups of reducing sugars. Previous studies have shown that highly glycated albumin prepared using a glucose-bovine serum albumin (Glu-BSA) model system incubated at 60°C for 6 weeks induces genotoxicity in WIL2-NS cells at 9 days of exposure measured by the cytokinesis-block micronucleus cytome (CBMNcyt) assay. However, this AGE model system is not physiologically relevant as normal body temperature is 37°C and the degree of glycation may exceed the extent of albumin modification in vivo. We hypothesised that the incubation temperature and purification method used in these studies may cause changes to the chemical profile of the glycated albumin and may influence the extent of genotoxicity observed at 3, 6 and 9 days of exposure. We prepared AGEs generated using Glu-BSA model systems incubated at 60°C or 37°C purified using trichloroacetic acid (TCA) precipitation or ultrafiltration (UF) and compared their chemical profile (glycation, oxidation, and aggregation) and genotoxicity in WIL2-NS cells using the CBMNcyt assay after 3, 6 and 9 days of exposure. The number of micronuclei (MNi) was significantly higher for cells treated with Glu-BSA incubated at 60°C and purified via TCA (12 ± 1 MNi/1000 binucleated cells) compared to Glu-BSA incubated at 37°C and purified using UF (6 ± 1 MNi/1000 binucleated cells) after 9 days (P < 0.0001). The increase in genotoxicity observed could be explained by a higher level of protein glycation, oxidation, and aggregation of the Glu-BSA model system incubated at 60°C relative to 37°C. This study highlighted that the incubation temperature, purification method and cell exposure time are important variables to consider when generating AGEs in vitro and will enable future studies to better reflect in vivo situations of albumin glycation.","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"36 6","pages":"445-455"},"PeriodicalIF":2.7,"publicationDate":"2021-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39491125","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}

引用次数: 1

Biomarkers of DNA damage response improve in vitro micronucleus assays by revealing genotoxic mode of action and reducing the occurrence of irrelevant positive results. DNA损伤反应的生物标志物通过揭示基因毒性作用模式和减少不相关阳性结果的发生来改善体外微核检测。

IF 2.7 4区医学

Mutagenesis Pub Date : 2021-11-29 DOI: 10.1093/mutage/geab039

Svetlana Avlasevich, Tina Pellegrin, Manali Godse, Steven Bryce, Jeffrey Bemis, Peter Bajorski, Stephen Dertinger

{"title":"Biomarkers of DNA damage response improve in vitro micronucleus assays by revealing genotoxic mode of action and reducing the occurrence of irrelevant positive results.","authors":"Svetlana Avlasevich, Tina Pellegrin, Manali Godse, Steven Bryce, Jeffrey Bemis, Peter Bajorski, Stephen Dertinger","doi":"10.1093/mutage/geab039","DOIUrl":"https://doi.org/10.1093/mutage/geab039","url":null,"abstract":"We have previously described two flow cytometry-based in vitro genotoxicity tests: micronucleus (MN) scoring (MicroFlow®) and a multiplexed DNA damage response biomarker assay (MultiFlow®). Here, we describe a strategy for combining the assays in order to efficiently supplement MN analyses with a panel of biomarkers that comment on cytotoxicity (i.e. relative nuclei count, relative increased nuclei count, cleaved PARP-positive chromatin and ethidium monoazide-positive chromatin) and genotoxic mode of action (MoA; i.e. γH2AX, phospho-histone H3, p53 activation and polyploidy). For these experiments, human TK6 cells were exposed to each of 32 well-studied reference chemicals in 96-well plates for 24 continuous hours. The test chemicals were evaluated over a range of concentrations in the presence and absence of a rat liver S9-based metabolic activation system. MultiFlow assay data were acquired at 4 and 24 h, and micronuclei were scored at 24 h. Testing 32 chemicals in two metabolic activation arms translated into 64 a priori calls: 42 genotoxicants and 22 non-genotoxicants. The MN assay showed high sensitivity and moderate specificity (90% and 68%, respectively). When a genotoxic call required significant MN and MultiFlow responses, specificity increased to 95% without adversely affecting sensitivity. The dose-response data were analysed with PROAST Benchmark Dose (BMD) software in order to calculate potency metrics for each endpoint, and ToxPi software was used to synthesise the resulting lower and upper bound 90% confidence intervals into visual profiles. The BMD/ToxPi combination was found to represent a powerful strategy for synthesising multiple BMD confidence intervals, as the software output provided MoA information as well as insights into genotoxic potency.","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"36 6","pages":"407-418"},"PeriodicalIF":2.7,"publicationDate":"2021-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633886/pdf/geab039.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39577106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Evaluation of the liver and blood micronucleus, and comet assay end points in a 14-day repeated-dose study with methyl carbamate and 1,3-propane sultone. 在一项为期14天的氨基甲酸甲酯和1,3-丙烷磺酮重复剂量研究中评估肝脏和血液微核和彗星试验终点。

IF 2.7 4区医学

Mutagenesis Pub Date : 2021-11-29 DOI: 10.1093/mutage/geab034

Honggang Tu, Chunrong Yu, Wen Tong, Changhui Zhou, Ruowan Li, Pengcheng Huang, Qingli Wang, Yan Chang

{"title":"Evaluation of the liver and blood micronucleus, and comet assay end points in a 14-day repeated-dose study with methyl carbamate and 1,3-propane sultone.","authors":"Honggang Tu, Chunrong Yu, Wen Tong, Changhui Zhou, Ruowan Li, Pengcheng Huang, Qingli Wang, Yan Chang","doi":"10.1093/mutage/geab034","DOIUrl":"https://doi.org/10.1093/mutage/geab034","url":null,"abstract":"The repeated-dose liver micronucleus (RDLMN) assay is a novel method for detecting genotoxic chemicals. Two carcinogens methyl carbamate (MC) and 1,3-propane sultone (PS) were evaluated for the liver micronucleus in a 14-day repeated-dose study with Crl: CD (SD) IGS rats. Additionally, micronucleated reticulocytes (MN-RET) in peripheral blood and DNA damage (alkaline comet assay) in the liver were also assessed in the same animals. Ten groups of five male Crl: CD (SD) IGS rats were treated once daily with MC (300, 600 or 1200 mg/kg/day), PS (37.5, 75 or 150 mg/kg/day), negative control or three positive controls by oral gavage for 15 days. Blood samples were collected at 3 h after the last administration for determining MN-RET frequencies (%MN-RET), and the livers were sampled for determining the frequency of micronuclei and DNA damage. MC was negative in the comet assay, liver micronucleus assay and reticulocyte micronucleus assay, while PS was positive in all three assays. These results are consistent with the previous genotoxic findings of MC and PS. Therefore, the liver micronucleus assay can be effectively integrated into repeated-dose studies in animals. Moreover, integration of multiple genotoxicity end points into one study can reduce the number of animals, boost the experimental efficiency, and provides a comprehensive evaluation of the genotoxic potential of chemicals.","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"36 6","pages":"401-406"},"PeriodicalIF":2.7,"publicationDate":"2021-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39412116","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}

引用次数: 1

Upregulation of mNEIL3 in Ogg1-null cells is a potential backup mechanism for 8-oxoG repair. 在Ogg1-null细胞中，mNEIL3的上调是8-oxoG修复的潜在备份机制。

IF 2.7 4区医学

Mutagenesis Pub Date : 2021-11-29 DOI: 10.1093/mutage/geab038

Ellen B Higgs, Roger Godschalk, Sabine A S Langie, Frederik-Jan van Schooten, Nikolas J Hodges

{"title":"Upregulation of mNEIL3 in Ogg1-null cells is a potential backup mechanism for 8-oxoG repair.","authors":"Ellen B Higgs, Roger Godschalk, Sabine A S Langie, Frederik-Jan van Schooten, Nikolas J Hodges","doi":"10.1093/mutage/geab038","DOIUrl":"https://doi.org/10.1093/mutage/geab038","url":null,"abstract":"Reactive oxygen species formation and resultant oxidative damage to DNA are ubiquitous events in cells, the homeostasis of which can be dysregulated in a range of pathological conditions. Base excision repair (BER) is the primary repair mechanism for oxidative genomic DNA damage. One prevalent oxidised base modification, 8-oxoguanine (8-oxoG), is recognised by 8-oxoguanine glycosylase-1 (OGG1) initiating removal and repair via BER. Surprisingly, Ogg1 null mouse embryonic fibroblasts (mOgg1-/- MEFs) do not accumulate 8-oxoG in the genome to the extent expected. This suggests that there are backup repair mechanisms capable of repairing 8-oxoG in the absence of OGG1. In the current study, we identified components of NER (Ercc1, Ercc4, Ercc5), BER (Lig1, Tdg, Nthl1, Mpg, Mgmt, NEIL3), MMR (Mlh1, Msh2, Msh6) and DSB (Brip1, Rad51d, Prkdc) pathways that are transcriptionally elevated in mOgg1-/- MEFs. Interestingly, all three nucleotide excision repair genes identified: Ercc1 (2.5 ± 0.2-fold), Ercc4 (1.5 ± 0.1-fold) and Ercc5 (1.7 ± 0.2-fold) have incision activity. There was also a significant functional increase in NER activity (42.0 ± 7.9%) compared to WT MEFs. We also observed upregulation of both Neil3 mRNA (37.9 ± 1.6-fold) and protein in mOgg1-/- MEFs. This was associated with a 3.4 ± 0.4-fold increase in NEIL3 substrate sites in genomic DNA of cells treated with BSO, consistent with the ability of NEIL3 to remove 8-oxoG oxidation products from genomic DNA. In conclusion, we suggest that in Ogg1-null cells, upregulation of multiple DNA repair proteins including incision components of the NER pathway and Neil3 are important compensatory responses to prevent the accumulation of genomic 8-oxoG.","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"36 6","pages":"437-444"},"PeriodicalIF":2.7,"publicationDate":"2021-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39514086","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}

引用次数: 1

Erratum to: The effect of chronic dosing and p53 status on the genotoxicity of pro-oxidant chemicals in vitro. 勘误：长期用药和 p53 状态对体外促氧化剂化学物质遗传毒性的影响。

IF 2.7 4区医学

Mutagenesis Pub Date : 2021-10-06 DOI: 10.1093/mutage/geab029

Emrah Dural, Ume-Kulsoom Shah, Demi Pritchard, Katherine Emma Chapman, Shareen Heather Doak, Gareth James Scott Jenkins

引用次数: 0

Trichostatin A mitigates radiation-induced teratogenesis in C57Bl/6 mice. 曲古霉素A减轻C57Bl/6小鼠辐射致致畸。

IF 2.7 4区医学

Mutagenesis Pub Date : 2021-08-27 DOI: 10.1093/mutage/geab018

Teena Haritwal, Nikita Goyal, Noopur Gupta, Suhel Parvez, Paban K Agrawala

{"title":"Trichostatin A mitigates radiation-induced teratogenesis in C57Bl/6 mice.","authors":"Teena Haritwal, Nikita Goyal, Noopur Gupta, Suhel Parvez, Paban K Agrawala","doi":"10.1093/mutage/geab018","DOIUrl":"https://doi.org/10.1093/mutage/geab018","url":null,"abstract":"Radiation exposure in utero is known to lead to serious concerns to both the mother and children, including developmental anomalies in the children. In the recent past, trichostatin A, an HDAC (histone deacetylase) inhibitor and epigenetic modifier, has been shown to mitigate radiation-induced anomalies in the male reproductive system of C57BL/6 mice. Therefore, the current study was undertaken to evaluate the mitigating effects of trichostatin A (TSA) against radiation-induced developmental anomalies in mice. Foetuses of in utero whole-body gamma-irradiated mice during the active organogenesis period were examined for developmental anomalies at 8.5 and 18.5 days of gestation. In utero radiation exposure caused developmental anomalies like microcephaly, microphthalmia, gastroschisis and kinky tail besides prenatal mortality. TSA administration post-irradiation was observed to reduce 50% of prenatal mortality at E18.5 by reducing congenital and developmental anomalies. Observation of such results could be corroborated with the HDAC inhibitory potential of TSA knowing that developmental anomalies may have epigenetic origin. TSA, therefore, can be considered as a potential radiomitigator.","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"36 4","pages":"303-309"},"PeriodicalIF":2.7,"publicationDate":"2021-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39061860","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}

引用次数: 1

Genetic variations in 3'UTRs of SMUG1 and NEIL2 genes modulate breast cancer risk, survival and therapy response. SMUG1和NEIL2基因3' utr的遗传变异调节乳腺癌的风险、生存和治疗反应。

IF 2.7 4区医学

Mutagenesis Pub Date : 2021-08-27 DOI: 10.1093/mutage/geab017

Andrea Cumova, Veronika Vymetalkova, Alena Opattova, Veronika Bouskova, Barbara Pardini, Katerina Kopeckova, Renata Kozevnikovova, Katerina Lickova, Miloslav Ambrus, Ludmila Vodickova, Alessio Naccarati, Pavel Soucek, Pavel Vodicka

{"title":"Genetic variations in 3'UTRs of SMUG1 and NEIL2 genes modulate breast cancer risk, survival and therapy response.","authors":"Andrea Cumova, Veronika Vymetalkova, Alena Opattova, Veronika Bouskova, Barbara Pardini, Katerina Kopeckova, Renata Kozevnikovova, Katerina Lickova, Miloslav Ambrus, Ludmila Vodickova, Alessio Naccarati, Pavel Soucek, Pavel Vodicka","doi":"10.1093/mutage/geab017","DOIUrl":"https://doi.org/10.1093/mutage/geab017","url":null,"abstract":"Breast cancer (BC) is the most frequent malignancy in women accounting for approximately 2 million new cases worldwide annually. Several genetic, epigenetic and environmental factors are known to be involved in BC development and progression, including alterations in post-transcriptional gene regulation mediated by microRNAs (miRNAs). Single nucleotide polymorphisms (SNPs) located in miRNA binding sites (miRSNPs) in 3'-untranslated regions of target genes may affect miRNA-binding affinity and consequently modulate gene expression. We have previously reported a significant association of miRSNPs in the SMUG1 and NEIL2 genes with overall survival in colorectal cancer patients. SMUG1 and NEIL2 are DNA glycosylases involved in base excision DNA repair. Assuming that certain genetic traits are common for solid tumours, we have investigated wherever variations in SMUG1 and NEIL2 genes display an association with BC risk, prognosis, and therapy response in a group of 673 BC patients and 675 healthy female controls. Patients with TC genotype of NEIL2 rs6997097 and receiving only hormonal therapy displayed markedly shorter overall survival (HR = 4.15, 95% CI = 1.7-10.16, P = 0.002) and disease-free survival (HR = 2.56, 95% CI = 1.5-5.7, P = 0.02). Our results suggest that regulation of base excision repair glycosylases operated by miRNAs may modulate the prognosis of hormonally treated BC.","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"36 4","pages":"269-279"},"PeriodicalIF":2.7,"publicationDate":"2021-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39069767","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}

引用次数: 4

Comparative potency analysis of whole smoke solutions in the bacterial reverse mutation test. 细菌反向突变试验中全烟雾溶液的效力比较分析。

IF 2.5 4区医学

Mutagenesis Pub Date : 2021-08-27 DOI: 10.1093/mutage/geab021

Fanxue Meng, Nan Mei, Jian Yan, Xiaoqing Guo, Patricia A Richter, Tao Chen, Mamata De

{"title":"Comparative potency analysis of whole smoke solutions in the bacterial reverse mutation test.","authors":"Fanxue Meng, Nan Mei, Jian Yan, Xiaoqing Guo, Patricia A Richter, Tao Chen, Mamata De","doi":"10.1093/mutage/geab021","DOIUrl":"10.1093/mutage/geab021","url":null,"abstract":"Short-term in vitro genotoxicity assays are useful tools to assess whether new and emerging tobacco products potentially have reduced toxicity. We previously demonstrated that potency ranking by benchmark dose (BMD) analysis quantitatively identifies differences among several known carcinogens and toxic chemicals representing different chemical classes found in cigarette smoke. In this study, six whole smoke solution (WSS) samples containing both the particulate and gas phases of tobacco smoke were generated from two commercial cigarette brands under different smoking-machine regimens. Sixty test cigarettes of each brand were machine-smoked according to the International Organization for Standardization (ISO) puffing protocol. In addition, either 60 or 20 test cigarettes of each brand were machine-smoked with the Canadian Intense (CI) puffing protocol. All six WSSs were evaluated in the bacterial reverse mutation (Ames) test using Salmonella typhimurium strains, in the presence or absence of S9 metabolic activation. The resulting S9-mediated mutagenic concentration-responses for the four WSSs from 60 cigarettes were then compared using BMD modelling analysis and the mutagenic potency expressed as number of revertants per μl of the WSS. The quantitative approaches resulted in a similar rank order of mutagenic potency for the Ames test in both TA98 and TA100. Under the conditions of this study, these results indicate that quantitative analysis of the Ames test data can discriminate between the mutagenic potencies of WSSs on the basis of smoking-machine regimen (ISO vs. CI), and cigarette product (differences in smoke chemistry).","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"36 4","pages":"321-329"},"PeriodicalIF":2.5,"publicationDate":"2021-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742878/pdf/nihms-1767369.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39235511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0