MutagenesisPub Date : 2023-02-03DOI: 10.1093/mutage/geac024
Jovana Jovanović Marić, Stoimir Kolarević, Jelena Đorđević, Karolina Sunjog, Ivan Nikolić, Ana Marić, Marija Ilić, Predrag Simonović, Nikiforos Alygizakis, Kelsey Ng, Peter Oswald, Jaroslav Slobodnik, Bojana Žegura, Branka Vuković-Gačić, Momir Paunović, Margareta Kračun-Kolarević
{"title":"In situ detection of the genotoxic potential as one of the lines of evidence in the weight-of-evidence approach-the Joint Danube Survey 4 Case Study.","authors":"Jovana Jovanović Marić, Stoimir Kolarević, Jelena Đorđević, Karolina Sunjog, Ivan Nikolić, Ana Marić, Marija Ilić, Predrag Simonović, Nikiforos Alygizakis, Kelsey Ng, Peter Oswald, Jaroslav Slobodnik, Bojana Žegura, Branka Vuković-Gačić, Momir Paunović, Margareta Kračun-Kolarević","doi":"10.1093/mutage/geac024","DOIUrl":"https://doi.org/10.1093/mutage/geac024","url":null,"abstract":"<p><p>Environmental studies which aim to assess the ecological impact of chemical and other types of pollution should employ a complex weight-of-evidence approach with multiple lines of evidence (LoEs). This study focused on in situ genotoxicological methods such as the comet and micronucleus assays and randomly amplified polymorphic DNA analysis as one of the multiple LoEs (LoE3) on the fish species Alburnus alburnus (bleak) as a bioindicator. The study was carried out within the Joint Danube Survey 4 (JDS4) at nine sites in the Danube River Basin in the Republic of Serbia. Out of nine sampling sites, two were situated at the Tisa, Sava, and Velika Morava rivers, and three sites were at the Danube River. The three additionally employed LoEs were: SumTUwater calculated based on the monitoring data in the database of the Serbian Environmental Protection Agency (SEPA) (LoE1); in vitro analyses of JDS4 water extracts employing genotoxicological methods (LoE2); assessment of the ecological status/potential by SEPA and indication of the ecological status for the sites performed within the JDS4 (LoE4). The analyzed biomarker responses in the bleak were integrated into the unique integrated biomarker response index which was used to rank the sites. The highest pollution pressure was recorded at JDS4 39 and JDS4 36, while the lowest was at JDS4 35. The impact of pollution was confirmed at three sites, JDS4 33, 40, and 41, by all four LoEs. At other sampling sites, a difference was observed regarding the pollution depending on the employed LoEs. This indicates the importance of implementing a comprehensive weight-of-evidence approach to ensure the impact of pollution is not overlooked when using only one LoE as is often the case in environmental studies.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 1","pages":"21-32"},"PeriodicalIF":2.7,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9295734","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":"A pilot biomonitoring study of air pollution in the urban area of Sarajevo, Bosnia and Herzegovina: genotoxicity assessment in buccal cells.","authors":"Tamara Cetkovic, Anja Haveric, Selma Behmen, Maida Hadzic Omanovic, Lejla Caluk Klacar, Alen Dzaferspahic, Irma Durmisevic, Mahira Mehanovic, Sanin Haveric","doi":"10.1093/mutage/geac016","DOIUrl":"https://doi.org/10.1093/mutage/geac016","url":null,"abstract":"<p><p>Air pollution, recognized as a human carcinogen, is a significant cause of death in industrial and developing countries, and Bosnia and Herzegovina (B&H) is one of the leading countries for air pollution-caused death rate and has the poorest urban air quality in Europe. Despite a population decrease, urban air pollution in B&H has increased due to traffic pollution and still intensive use of solid fuel for heating and cooking. Human biomonitoring studies, regarding the described air pollution, have not been conducted before, and particularly have not been conducted in the region of Sarajevo. Good health, well-being, and environmental protection are part of the 17 defined Sustainable Development Global Goals. Accordingly, this study aimed to determine baseline levels of DNA damage in a group of Sarajevo citizens and to compare seasonal variations in DNA damage in relation to the reported levels of air pollution. From 33 individuals included in the study, samples were collected in the summer and winter seasons. The buccal micronucleus cytome (BMCyt) assay and comet assay in leucocytes isolated from saliva were performed. Mean values and standard deviations of log-transformed tail intensity (%), tail length (µm), and tail moment results in winter were 1.14 ± 0.23, 2.20 ± 0.14, and 1.03 ± 0.29, respectively, while in the summer season those values were 1.19 ± 0.19, 2.25 ± 0.17, and 1.07 ± 0.25, respectively. No significant differences were found for the comet assay parameters. Nevertheless, BMCyt results showed significant increases in micronuclei (P = .008), binuclear cells (P = .04), karyolysis (P = .0003), condensed chromatin (P = .03), and pyknosis (P = .002) in winter. Although the results of comet and BMCyt assays are not in accordance, this study contributes to the human air pollution biomonitoring in Sarajevo, B&H, and based on the genotoxic effects of air pollution evidenced by the BMCyt biomarker further studies of this kind are necessary.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 1","pages":"33-42"},"PeriodicalIF":2.7,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9279667","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}
MutagenesisPub Date : 2023-02-03DOI: 10.1093/mutage/geac023
Deni Kostelac, Marko Gerić, Goran Gajski, Jadranka Frece
{"title":"Probiotic bacteria isolated from fermented meat displays high antioxidant and anti-inflammatory potential.","authors":"Deni Kostelac, Marko Gerić, Goran Gajski, Jadranka Frece","doi":"10.1093/mutage/geac023","DOIUrl":"https://doi.org/10.1093/mutage/geac023","url":null,"abstract":"<p><p>One of the ways to impact emerging problems of unhealthy diet such as microbiota dysbiosis, inflammation, and oxidative stress is the application of probiotics and their incorporation into different food matrices. Discovery and selection of appropriate probiotic bacteria is challenging procedure especially for fermented meat products that have also been described as a potential source of resilient probiotic microorganisms. The aim of this study was to investigate probiotic bacteria Lactiplantibacillus plantarum 1K isolated from traditional fermented meat product for its potential beneficial properties. Furthermore, small probiotic metabolites were extracted, and their anti-inflammatory activity was tested in a lipopolysaccharide-stimulated inflammatory model on human peripheral blood mononuclear cells (PBMCs). Safety characteristics of metabolites including cytotoxicity and genotoxicity were also determined. Investigated probiotic strain exerted high antioxidant potential by viable cells but also by metabolite fraction. Viable cells retained the satisfactory antioxidant activity after gastrointestinal transit. Extracted probiotic metabolites significantly inhibited TNF-α production in LPS-stimulated PBMC thus exerting anti-inflammatory activity. Metabolites alone showed no cytotoxic or genotoxic activity toward isolated immune cells. Obtained results indicate the possibility to use fermented meat products as sources for specific probiotics that might provide antioxidant and anti-inflammatory benefits for the consumers.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 1","pages":"58-63"},"PeriodicalIF":2.7,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10729743","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}
MutagenesisPub Date : 2023-02-03DOI: 10.1093/mutage/geac013
Marija Bruić, Andrea Pirković, Aleksandra Vilotić, Milica Jovanović-Krivokuća, Biljana Spremo-Potparević
{"title":"Cytoprotective and genoprotective effects of taxifolin against oxidative damage in HTR-8/SVneo human trophoblast cells.","authors":"Marija Bruić, Andrea Pirković, Aleksandra Vilotić, Milica Jovanović-Krivokuća, Biljana Spremo-Potparević","doi":"10.1093/mutage/geac013","DOIUrl":"https://doi.org/10.1093/mutage/geac013","url":null,"abstract":"<p><p>An increase of reactive oxygen species in the placenta and oxidative disbalance has been recognized as a significant factor contributing to pregnancy complications. Dietary intake of food rich in antioxidants during pregnancy could exert a protective role in the prevention of adverse outcomes such as preeclampsia, miscarriage, and others. Flavonoid taxifolin has shown numerous health-promoting effects in a large number of studies conducted on animals, as well as various human cell types in vitro. However, its effects on human placental cells-trophoblasts-have yet to be determined. Therefore, cytoprotective and genoprotective effects of taxifolin on trophoblast cell line HTR-8/SVneo under induced oxidative stress were explored in this study. Cytotoxicity of a range of taxifolin concentrations (1-150 µM) was evaluated using the MTT and crystal violet assays. A model of oxidative stress was achieved by exposing HTR-8/SVneo cells to H2O2. To determine cytoprotective and antigenotoxic effects, the cells were pre-incubated with three concentrations of taxifolin (10, 50, and 100 µM) and then exposed to H2O2. Taxifolin in concentrations of 1, 5, 10, 25, 50, and 100 µM showed no cytotoxic effects on HTR-8/SVneo cells, but 150 µM of taxifolin caused a significant decrease in adherent cell number, as detected by crystal violet assay. Pretreatment with the chosen concentrations of taxifolin showed a significant cytoprotective effect on H2O2-induced cytotoxicity, as determined by the MTT assay. Furthermore, taxifolin showed a significant reduction in H2O2-induced DNA damage, measured by comet assay. This study showed protective effects of taxifolin on human trophoblast cells exposed to oxidative damage. Further studies are needed to explore the underlying mechanisms.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 1","pages":"64-70"},"PeriodicalIF":2.7,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10735070","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}
MutagenesisPub Date : 2023-02-03DOI: 10.1093/mutage/geac021
Julen Sanz-Serrano, Roncesvalles Garayoa, Ana Isabel Vitas, Adela López de Cerain, Amaya Azqueta
{"title":"In vitro genotoxicity assessment of French fries from mass catering companies: a preliminary study.","authors":"Julen Sanz-Serrano, Roncesvalles Garayoa, Ana Isabel Vitas, Adela López de Cerain, Amaya Azqueta","doi":"10.1093/mutage/geac021","DOIUrl":"https://doi.org/10.1093/mutage/geac021","url":null,"abstract":"<p><p>It is generally assumed that French fries are likely to have weak in vitro mutagenic activity, but most studies thereof have only assessed gene mutations. In this article, the genotoxicity of 10 extracts of French fries was assessed using the in vitro micronucleus test (following the principles of the OECD 487 guidelines). Each sample was obtained from a different mass catering company in Navarra (Spain). This assay, together with the Ames test, is recommended in the basic in vitro phase included in the European Food Safety Authority Opinion on Genotoxicity Testing Strategies Applicable to Food and Feed Safety Assessment. Eight of 10 samples from mass catering companies induced chromosomal aberrations in the in vitro micronucleus test. Moreover, French fries deep-fried in the laboratory for different periods of time (0, 3, 5, 10, 20, 30 min) were assessed using the in vitro micronucleus test. Genotoxicity was observed in all time periods from 3 min on. The biological relevance of these results must be further explored.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 1","pages":"51-57"},"PeriodicalIF":2.7,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9295226","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}
MutagenesisPub Date : 2023-02-03DOI: 10.1093/mutage/geac017
Stoimir Kolarević, Margareta Kračun-Kolarević, Jovana Jovanović Marić, Jelena Djordjević, Branka Vuković-Gačić, Danijela Joksimović, Rajko Martinović, Oliver Bajt, Andreja Ramšak
{"title":"Single and combined potential of polystyrene microparticles and fluoranthene in the induction of DNA damage in haemocytes of Mediterranean mussel (Mytilus galloprovincialis).","authors":"Stoimir Kolarević, Margareta Kračun-Kolarević, Jovana Jovanović Marić, Jelena Djordjević, Branka Vuković-Gačić, Danijela Joksimović, Rajko Martinović, Oliver Bajt, Andreja Ramšak","doi":"10.1093/mutage/geac017","DOIUrl":"https://doi.org/10.1093/mutage/geac017","url":null,"abstract":"<p><p>In this study, the possible 'vector effect' within the exposure of Mediterranean mussels (Mytilus galloprovincialis) to polystyrene microplastics with adsorbed fluoranthene was investigated by applying the multibiomarker approach. The major focus was placed on genotoxicological endpoints as to our knowledge there are no literature data on the genotoxicity of polystyrene microparticles alone or with adsorbed fluoranthene in the selected experimental organisms. DNA damage was assessed in haemocytes by comet assay and micronucleus test. For the assessment of neurotoxicity, acetylcholinesterase activity was measured in gills. Glutathione S-transferase was assessed in gills and hepatopancreas since these enzymes are induced for biotransformation and excretion of lipophilic compounds such as hydrocarbons. Finally, differences in physiological response within the exposure to polystyrene particles, fluoranthene, or particles with adsorbed fluoranthene were assessed by the variation of heart rate patterns studied by the noninvasive laser fibre-optic method. The uniform response of individual biomarkers within the exposure groups was not recorded. There was no clear pattern in variation of acetylcholinesterase or glutathione S-transferase activity which could be attributed to the treatment. Exposure to polystyrene increased DNA damage which was detected by the comet assay but was not confirmed by micronucleus formation. Data of genotoxicity assays indicated differential responses among the groups exposed to fluoranthene alone and fluoranthene adsorbed to polystyrene. Change in the heart rate patterns within the studied groups supports the concept of the Trojan horse effect within the exposure to polystyrene particles with adsorbed fluoranthene.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 1","pages":"3-12"},"PeriodicalIF":2.7,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10729196","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}
MutagenesisPub Date : 2023-02-03DOI: 10.1093/mutage/geac018
Fengjia Liu, Kim S Last, Theodore B Henry, Helena C Reinardy
{"title":"Interspecific differences in oxidative DNA damage after hydrogen peroxide exposure of sea urchin coelomocytes.","authors":"Fengjia Liu, Kim S Last, Theodore B Henry, Helena C Reinardy","doi":"10.1093/mutage/geac018","DOIUrl":"https://doi.org/10.1093/mutage/geac018","url":null,"abstract":"<p><p>Interspecific comparison of DNA damage can provide information on the relative vulnerability of marine organisms to toxicants that induce oxidative genotoxicity. Hydrogen peroxide (H2O2) is an oxidative toxicant that causes DNA strand breaks and nucleotide oxidation and is used in multiple industries including Atlantic salmon aquaculture to treat infestations of ectoparasitic sea lice. H2O2 (up to 100 mM) can be released into the water after sea lice treatment, with potential consequences of exposure in nontarget marine organisms. The objective of the current study was to measure and compare differences in levels of H2O2-induced oxidative DNA damage in coelomocytes from Scottish sea urchins Echinus esculentus, Paracentrotus lividus, and Psammechinus miliaris. Coelomocytes were exposed to H2O2 (0-50 mM) for 10 min, cell concentration and viability were quantified, and DNA damage was measured by the fast micromethod, an alkaline unwinding DNA method, and the modified fast micromethod with nucleotide-specific enzymes. Cell viability was >92% in all exposures and did not differ from controls. Psammechinus miliaris coelomocytes had the highest oxidative DNA damage with 0.07 ± 0.01, 0.08 ± 0.01, and 0.07 ± 0.01 strand scission factors (mean ± SD) after incubation with phosphate-buffered saline, formamidopyrimidine-DNA glycosylase, and endonuclease-III, respectively, at 50 mM H2O2. Exposures to 0.5 mM H2O2 (100-fold dilution from recommended lice treatment concentration) induced oxidative DNA damage in all three species of sea urchins, suggesting interspecific differences in vulnerabilities to DNA damage and/or DNA repair mechanisms. Understanding impacts of environmental genotoxicants requires understanding species-specific susceptibilities to DNA damage, which can impact long-term stability in sea urchin populations in proximity to aquaculture farms.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 1","pages":"13-20"},"PeriodicalIF":2.7,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10785206","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}
{"title":"Air pollution in Sarajevo, Bosnia and Herzegovina, assessed by plant comet assay.","authors":"Mujo Hasanovic, Tamara Cetkovic, Bertrand Pourrut, Lejla Caluk Klacar, Maida Hadzic Omanovic, Adaleta Durmic-Pasic, Sanin Haveric, Anja Haveric","doi":"10.1093/mutage/geac022","DOIUrl":"https://doi.org/10.1093/mutage/geac022","url":null,"abstract":"<p><p>Bosnia and Herzegovina (B&H) is among the European countries with the highest rate of air pollution-related death cases and the poorest air quality. The main causes are solid fuel consumption, traffic, and the poorly developed or implemented air pollution reduction policies. In addition, the city of Sarajevo, the capital of B&H, suffers temperature inversion episodes in autumn/winter months, which sustain air pollution. Human biomonitoring studies may be confounded by the lifestyle of subjects or possible metabolic alterations. Therefore, this study aimed to evaluate Ligustrum vulgare L. as a model for air pollution monitoring by measuring DNA damage at one rural and two urban sites. DNA damage was measured as tail intensity (TI) in L. vulgare leaves, considering seasonal, sampling period, leaf position and staging, and spatial (urban versus rural) variation. Effects of COVID-19 lockdown on TI were assessed by periodical monitoring at one of the selected sites, while in-house grown L. vulgare plants were used to test differences between outdoor and indoor air pollution effects for the same sampling period. Significantly higher TI was generally observed in leaves collected in Campus in December 2020 and 2021 compared with March (P < 0.0001). Outer and adult leaves showed higher TI values, except for the rural site where no differences for these categories were found. Leaves collected in the proximity of the intensive traffic showed significantly higher TI values (P < 0.001), regardless of the sampling period and the stage of growth. In regards to the COVID-19 lockdown, higher TI (P < 0.001) was registered in December 2020, after the lockdown period, than in periods before COVID-19 outbreak or immediately after the lockdown in 2020. This also reflects mild air pollution conditions in summer. TI values for the in-house grown leaves were significantly lower compared to those in situ. Results showed that L. vulgare may present a consistent model for the air pollution biomonitoring but further studies are needed to establish the best association between L. vulgare physiology, air quality data, and air pollution effects.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"38 1","pages":"43-50"},"PeriodicalIF":2.7,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9280191","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}
MutagenesisPub Date : 2022-12-08DOI: 10.1093/mutage/geac019
Xiuyi Pan, Junya Tan, Xiaoxue Yin, Qianqi Liu, Linmao Zheng, Zhengzheng Su, Qiao Zhou, Ni Chen
{"title":"The roles of mutated SPINK1 gene in prostate cancer cells.","authors":"Xiuyi Pan, Junya Tan, Xiaoxue Yin, Qianqi Liu, Linmao Zheng, Zhengzheng Su, Qiao Zhou, Ni Chen","doi":"10.1093/mutage/geac019","DOIUrl":"https://doi.org/10.1093/mutage/geac019","url":null,"abstract":"<p><p>SPINK1-positive prostate cancer (PCa) has been identified as an aggressive PCa subtype. However, there is a lack of definite studies to elucidate the underlying mechanism of the loss of SPINK1 expression in most PCa cells except 22Rv1 cells, which are derived from a human prostatic carcinoma xenograft, CWR22R. The aim of this study was to investigate the mechanisms of SPINK1 protein positive/negative expression and its biological roles in PCa cell lines. SPINK1 mRNA was highly expressed in 22Rv1 cells compared with LNCaP, C4-2B, DU145, and PC-3 cells, and the protein was only detected in 22Rv1 cells. Among these cell lines, the wild-type SPINK1 coding sequence was only found in 22Rv1 cells, and two mutation sites, the c.194G>A missense mutation and the c.210T>C synonymous mutation, were found in other cell lines. Our further research showed that the mutations were associated with a reduction in SPINK1 mRNA and protein levels. Functional experiments indicated that SPINK1 promoted PC-3 cell proliferation, migration, and invasion, while knockdown of SPINK1 attenuated 22Rv1 cell proliferation, migration, and invasion. The wild-type SPINK1 gene can promote the malignant behaviors of cells more than the mutated ones. Cell cycle analysis by flow cytometry showed that SPINK1 decreased the percentage of cells in the G0/G1 phase and increased the percentage of S phase cells. We demonstrated that the c.194G>A and c.210T>C mutations in the SPINK1 gene decreased the mRNA and protein levels. The wild-type SPINK1 gene is related to aggressive biological behaviors of PCa cells and may be a potential therapeutic target for PCa.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":"37 5-6","pages":"238-247"},"PeriodicalIF":2.7,"publicationDate":"2022-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10508234","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}