MutagenesisPub Date : 2024-04-24DOI: 10.1093/mutage/geae010
Michael J Burgum, Clarissa Ulrich, Natascha Partosa, Stephen J Evans, Caroline Gomes, Svenja Berit Seiffert, Robert Landsiedel, Naveed Honarvar, Shareen H Doak
{"title":"Adapting the in vitro micronucleus assay (OECD Test Guideline No. 487) for testing of manufactured nanomaterials: recommendations for best practices.","authors":"Michael J Burgum, Clarissa Ulrich, Natascha Partosa, Stephen J Evans, Caroline Gomes, Svenja Berit Seiffert, Robert Landsiedel, Naveed Honarvar, Shareen H Doak","doi":"10.1093/mutage/geae010","DOIUrl":"10.1093/mutage/geae010","url":null,"abstract":"<p><p>The current Organisation for Economic Co-Operation and Development test guideline number 487 (OECD TG No. 487) provides instruction on how to conduct the in vitro micronucleus assay. This assay is one of the gold standard approaches for measuring the mutagenicity of test items; however, it is directed at testing low molecular weight molecules and may not be appropriate for particulate materials (e.g. engineered nanoparticles [ENPs]). This study aimed to adapt the in vitro micronucleus assay for ENP testing and underpins the development of an OECD guidance document. A harmonized, nano-specific protocol was generated and evaluated by two independent laboratories. Cell lines utilized were human lymphoblastoid (TK6) cells, human liver hepatocytes (HepG2) cells, Chinese hamster lung fibroblast (V79) cells, whole blood, and buffy coat cells from healthy human volunteers. These cells were exposed to reference ENPs from the Joint Research Council (JRC): SiO2 (RLS-0102), Au5nm and Au30nm (RLS-03, RLS-010), CeO2 (NM212), and BaSO4 (NM220). Tungsten carbide-cobalt (WC/Co) was used as a trial particulate positive control. The chemical controls were positive in all cell cultures, but WC/Co was only positive in TK6 and buffy coat cells. In TK6 cells, mutagenicity was observed for SiO2- and both Au types. In HepG2 cells, Au5nm and SiO2 showed sub-two-fold increases in micronuclei. In V79 cells, whole blood, and buffy coat cells, no genotoxicity was detected with the test materials. The data confirmed that ENPs could be tested with the harmonized protocol, additionally, concordant data were observed across the two laboratories with V79 cells. WC/Co may be a suitable particulate positive control in the in vitro micronucleus assay when using TK6 and buffy coat cells. Detailed recommendations are therefore provided to adapt OECD TG No. 487 for testing ENP.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11040148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175589","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 : 2024-04-24DOI: 10.1093/mutage/geae002
Akhila Sankar, Ravi Kumar Y S, Anjali Singh, Riya Roy, Rashmi Shukla, Bhupendra Verma
{"title":"Next-generation therapeutics for rare genetic disorders.","authors":"Akhila Sankar, Ravi Kumar Y S, Anjali Singh, Riya Roy, Rashmi Shukla, Bhupendra Verma","doi":"10.1093/mutage/geae002","DOIUrl":"10.1093/mutage/geae002","url":null,"abstract":"<p><p>The therapeutic potential of the human genome has been explored through the development of next-generation therapeutics, which have had a high impact on treating genetic disorders. Classical treatments have traditionally focused on common diseases that require repeated treatments. However, with the recent advancements in the development of nucleic acids, utilizing DNA and RNA to modify or correct gene expression in genetic disorders, there has been a paradigm shift in the treatment of rare diseases, offering more potential one-time cure options. Advanced technologies that use CRISPR-Cas 9, antisense oligonucleotides, siRNA, miRNA, and aptamers are promising tools that have achieved successful breakthroughs in the treatment of various genetic disorders. The advancement in the chemistry of these molecules has improved their efficacy, reduced toxicity, and expanded their clinical use across a wide range of tissues in various categories of human disorders. However, challenges persist regarding the safety and efficacy of these advanced technologies in translating into clinical practice. This review mainly focuses on the potential therapies for rare genetic diseases and considers how next-generation techniques enable drug development to achieve long-lasting curative effects through gene inhibition, replacement, and editing.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139707281","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 : 2024-04-24DOI: 10.1093/mutage/geae003
Aleksandra Marković, Darko Grujičić, Marija Živković Radojević, Olivera Milošević-Djordjević
{"title":"Measurement of chromosomal instability and level of DNA damage in peripheral blood mononuclear cells of endometrial cancer patients.","authors":"Aleksandra Marković, Darko Grujičić, Marija Živković Radojević, Olivera Milošević-Djordjević","doi":"10.1093/mutage/geae003","DOIUrl":"10.1093/mutage/geae003","url":null,"abstract":"<p><p>Endometrial cancer is one of the most common invasive gynecologic malignancies in developed countries. The aim of this study was to evaluate chromosomal instability and level of DNA damage in peripheral blood mononuclear cells (PBMCs) of newly diagnosed endometrial cancer patients in relation to health status (diagnosis), age, histological grade of cancer, residence, smoking, number of pregnancies, miscarriages, and abortions. The analyzed sample consisted of 60 individuals, 30 endometrial cancer patients with an average age of 64.37 ± 7.08, and 30 healthy control women with an average age of 60.23 ± 11.55. Chromosomal instability was evaluated by the cytokinesis-block micronucleus (CBMN) assay, and the level of DNA damage by the single-cell gel electrophoresis (comet) assay in PBMCs. The average frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs) as well as nuclear buds (NBUDs) were significantly higher in cancer patients compared to controls (P < .0005). There was no difference in the nuclear division index (NDI) among the analyzed samples. The comet assay showed that the patients had a significantly increased genetic damage index (GDI) compared with controls (P < .0005). Using linear regression analysis, we found that health status (diagnosis) had the strongest influence on the MN frequency as well as GDI (P < .0005). Our results indicated that there is a high level of genetic damage in both the level of DNA and the level of chromosomes in the PBMCs of newly diagnosed patients with endometrial cancer, where the frequency and level of damage were significantly affected by health status, grade of cancer, residence, number of pregnancies, miscarriages, and abortions.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139546674","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 : 2024-04-24DOI: 10.1093/mutage/geae005
Hang Wu, Ya Xu, Yun Yun Gong, John Huntriss, Michael N Routledge
{"title":"Effects of aflatoxin and fumonisin on gene expression of growth factors and inflammation-related genes in a human hepatocyte cell line.","authors":"Hang Wu, Ya Xu, Yun Yun Gong, John Huntriss, Michael N Routledge","doi":"10.1093/mutage/geae005","DOIUrl":"10.1093/mutage/geae005","url":null,"abstract":"<p><p>Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are mycotoxins widely distributed in maize and maized-based products, often occurring together. The implications of co-exposure to aflatoxin and fumonsin for human health are numerous, but a particular concern is the potential of FB1 to modulate AFB1 hepatotoxicity. This study evaluated the toxicity of these mycotoxins, alone or combined, in a human non-tumorigenic liver cell line, HHL-16 cells, and assessed the effects of AFB1 and FB1 on expression of genes involved in immune and growth factor pathways. The results demonstrated that in HHL-16 cells, both AFB1 and FB1 had dose-dependent and time-dependent toxicity, and the combination of them showed a synergistic toxicity in the cells. Moreover, AFB1 caused upregulation of IL6, CCL20, and BMP2, and downregulation of NDP. In combination of AFB1 with FB1, gene expression levels of IL6 and BMP2 were significantly higher compared to individual FB1 treatment, and had a tendency to be higher than individual AFB1 treatment. This study shows that FB1 may increase the hepatoxicity of AFB1 through increasing the inflammatory response and disrupting cell growth pathways.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11040159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140102048","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 : 2024-04-24DOI: 10.1093/mutage/geae007
Dieuwertje E Kok, Rachael Saunders, Andrew Nelson, Darren Smith, Dianne Ford, John C Mathers, Jill A McKay
{"title":"Influence of maternal folate depletion on Art3 DNA methylation in the murine adult brain; potential consequences for brain and neurocognitive health.","authors":"Dieuwertje E Kok, Rachael Saunders, Andrew Nelson, Darren Smith, Dianne Ford, John C Mathers, Jill A McKay","doi":"10.1093/mutage/geae007","DOIUrl":"10.1093/mutage/geae007","url":null,"abstract":"<p><p>The developmental origins of health and disease hypothesis suggest early-life environment impacts health outcomes throughout the life course. In particular, epigenetic marks, including DNA methylation, are thought to be key mechanisms through which environmental exposures programme later-life health. Adequate maternal folate status before and during pregnancy is essential in the protection against neural tube defects, but data are emerging that suggest early-life folate exposures may also influence neurocognitive outcomes in childhood and, potentially, thereafter. Since folate is key to the supply of methyl donors for DNA methylation, we hypothesize that DNA methylation may be a mediating mechanism through which maternal folate influences neurocognitive outcomes. Using bisulphite sequencing, we measured DNA methylation of five genes (Art3, Rsp16, Tspo, Wnt16, and Pcdhb6) in the brain tissue of adult offspring of dams who were depleted of folate (n = 5, 0.4 mg folic acid/kg diet) during pregnancy (~19-21 days) and lactation (mean 22 days) compared with controls (n = 6, 2 mg folic acid/kg diet). Genes were selected as methylation of their promoters had previously been found to be altered by maternal folate intake in mice and humans across the life course, and because they have potential associations with neurocognitive outcomes. Maternal folate depletion was significantly associated with Art3 gene hypomethylation in subcortical brain tissue of adult mice at 28 weeks of age (mean decrease 6.2%, P = .03). For the other genes, no statistically significant differences were found between folate depleted and control groups. Given its association with neurocognitive outcomes, we suggest Art3 warrants further study in the context of lifecourse brain health. We have uncovered a potential biomarker that, once validated in accessible biospecimens and human context, may be useful to track the impact of early-life folate exposure on later-life neurocognitive health, and potentially be used to develop and monitor the effects of interventions.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11040152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990670","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 : 2024-04-12DOI: 10.1093/mutage/geae012
M Giaccherini, M Rende, M Gentiluomo, C Corradi, L Archibugi, S Ermini, E Maiello, L Morelli, C H J van Eijck, G M Cavestro, M Schneider, A Mickevicius, K Adamonis, D Basso, V Hlavac, D Gioffreda, R Talar-Wojnarowska, B Schöttker, M Lovecek, G Vanella, M Gazouli, M Uno, E Malecka-Wojciesko, P Vodicka, M Goetz, M F Bijlsma, M C Petrone, F Bazzocchi, M Kiudelis, A Szentesi, S Carrara, G Nappo, H Brenner, A C Milanetto, P Soucek, V Katzke, G Peduzzi, C Rizzato, C Pasquali, X Chen, G Capurso, T Hackert, B Bueno-de-Mesquita, F G G Uzunoglu, P Hegyi, W Greenhalf, G E E Theodoropoulos, C Sperti, F Perri, M Oliverius, A Mambrini, F Tavano, R Farinella, P G Arcidiacono, M Lucchesi, S Bunduc, J Kupcinskas, G Di Franco, S Stocker, J P Neoptolemos, F Bambi, K Jamroziak, S G G Testoni, M N Aoki, B Mohelnikova-Duchonova, J R Izbicki, R Pezzilli, R T Lawlor, E F Kauffmann, E López de Maturana, N Malats, F Canzian, D Campa
{"title":"A pleiotropy scan to discover new susceptibility loci for pancreatic ductal adenocarcinoma","authors":"M Giaccherini, M Rende, M Gentiluomo, C Corradi, L Archibugi, S Ermini, E Maiello, L Morelli, C H J van Eijck, G M Cavestro, M Schneider, A Mickevicius, K Adamonis, D Basso, V Hlavac, D Gioffreda, R Talar-Wojnarowska, B Schöttker, M Lovecek, G Vanella, M Gazouli, M Uno, E Malecka-Wojciesko, P Vodicka, M Goetz, M F Bijlsma, M C Petrone, F Bazzocchi, M Kiudelis, A Szentesi, S Carrara, G Nappo, H Brenner, A C Milanetto, P Soucek, V Katzke, G Peduzzi, C Rizzato, C Pasquali, X Chen, G Capurso, T Hackert, B Bueno-de-Mesquita, F G G Uzunoglu, P Hegyi, W Greenhalf, G E E Theodoropoulos, C Sperti, F Perri, M Oliverius, A Mambrini, F Tavano, R Farinella, P G Arcidiacono, M Lucchesi, S Bunduc, J Kupcinskas, G Di Franco, S Stocker, J P Neoptolemos, F Bambi, K Jamroziak, S G G Testoni, M N Aoki, B Mohelnikova-Duchonova, J R Izbicki, R Pezzilli, R T Lawlor, E F Kauffmann, E López de Maturana, N Malats, F Canzian, D Campa","doi":"10.1093/mutage/geae012","DOIUrl":"https://doi.org/10.1093/mutage/geae012","url":null,"abstract":"Pleiotropic variants (i.e., genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleiotropic variants was successfully conducted ten years ago in relation to pancreatic ductal adenocarcinoma susceptibility. However, in the last decade, genetic association studies performed on several human traits have greatly increased the number of known pleiotropic variants. Based on the hypothesis that variants already associated with a least one trait have a higher probability of association with other traits, 61,052 variants reported to be associated by at least one genome wide association study (GWAS) with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16,055 pancreatic ductal adenocarcinoma (PDAC) cases and 212,149 controls. The meta-analysis of the two phases showed two loci (10q21.1-rs4948550 (P=6.52×10-5) and 7q36.3-rs288762 (P=3.03×10-5) potentially associated with PDAC risk. 10q21.1-rs4948550 shows a high degree of pleiotropy and it is also associated with colorectal cancer risk while 7q36.3-rs288762 is situated 28,558 base pairs upstream of the Sonic Hedgehog (SHH) gene, which is involved in the cell differentiation process and PDAC etiopathogenesis. In conclusion, none of the single nucleotide polymorphisms (SNPs) showed a formally statistically significant association after correction for multiple testing. However, given their pleiotropic nature and association with various human traits including colorectal cancer, the two SNPs showing the best associations with PDAC risk merit further investigation through fine mapping and ad hoc functional studies.","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586454","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 : 2024-03-29DOI: 10.1093/mutage/geae009
Pavel Vodicka, Ludmila Vodickova
{"title":"Commentary: Special Issue - Current Understanding of Colorectal and Pancreatic Cancers.","authors":"Pavel Vodicka, Ludmila Vodickova","doi":"10.1093/mutage/geae009","DOIUrl":"https://doi.org/10.1093/mutage/geae009","url":null,"abstract":"<p><p>The Commentary on Special Issue- Current Understanding of Colorectal and Pancreatic Cancers provides the reasoning for the selection of the contributions on pancreatic and colorectal cancer, and summarizes in brief the individual topics and comments upon the main outcomes. The current knowledge, contribution of the individual articles within this Special Issue, and arising priorities in the research on pancreatic ductal adenocarcinoma and colorectal cancer are highlighted.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140326883","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 : 2024-03-23DOI: 10.1093/mutage/geae011
S L Hernández-Ojeda, J J Espinosa-Aguirre, R Camacho Carranza, J Amacosta-Castillo, R I Cárdenas-Ávila
{"title":"Piper auritum ethanol extract is a potent antimutagen against food-borne aromatic amines. Mechanisms of action and chemical composition.","authors":"S L Hernández-Ojeda, J J Espinosa-Aguirre, R Camacho Carranza, J Amacosta-Castillo, R I Cárdenas-Ávila","doi":"10.1093/mutage/geae011","DOIUrl":"https://doi.org/10.1093/mutage/geae011","url":null,"abstract":"<p><p>An ethanol extract of Piper auritum leaves (PAEE) inhibits the mutagenic effect of three food-borne aromatic amines (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP); 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx); 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) in the TA98 Salmonella typhimurium strain. Preincubation with MeIQx demonstrated in mutagenesis experiments that inhibition of Cytochrome P450 (CYP), as well as direct interaction between component(s) of the plant extract with mutagens, might account for the antimutagenic observed effect. Gas chromatography/mass spectrometry analysis revealed that safrole (50.7%), α-copaene (7.7%), caryophyllene (7.2%), β-pinene (4.2%), γ-terpinene (4.1%) and pentadecane (4.1%) as the main components of PAEE. Piper extract and safrole were able to inhibit the rat liver microsomal CYP1A1 activity that participates in the amines metabolism, leading to the formation of the ultimate mutagenic/ molecules. According to this, safrole and PAEE inhibited MeIQx mutagenicity but not that of the direct mutagen 2-nitrofluorene. No mutagenicity of plant extract or safrole was detected. This study show that PAEE and its main component safrole are associate with the inhibition of heterocyclic amines activation due in part to the inhibition of CYP1A subfamily activity.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194216","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 : 2024-03-12DOI: 10.1093/mutage/gead035
Marina Lummertz Magenis, Adriani Paganini Damiani, Isadora de Oliveira Monteiro, Ligia Salvan Dagostin, Nicollas Dos Santos Silva, Rahisa Scussel, Seigo Nagashima, Sabine A S Langie, Ricardo Aurino Pinho, Vanessa Moraes de Andrade
{"title":"Maternal exercise during pregnancy modulates genotoxicity caused by high fructose consumption in mice offspring.","authors":"Marina Lummertz Magenis, Adriani Paganini Damiani, Isadora de Oliveira Monteiro, Ligia Salvan Dagostin, Nicollas Dos Santos Silva, Rahisa Scussel, Seigo Nagashima, Sabine A S Langie, Ricardo Aurino Pinho, Vanessa Moraes de Andrade","doi":"10.1093/mutage/gead035","DOIUrl":"10.1093/mutage/gead035","url":null,"abstract":"<p><p>Pregnancy is a period that is characterized by several metabolic and physiological changes and requires special attention, especially with regard to the relationship between feeding and foetal development. Therefore, the objective of this study was to evaluate whether the practice of voluntary physical exercise (VPE) in combination with chronic consumption of fructose (FRU) from the beginning of life and/or until the gestational period causes genotoxic changes in pregnant females and in their offspring. Seventy Swiss female mice received FRU in the hydration bottle and/or practiced VPE for 8 weeks (prepregnancy/pregnancy). After the lactation period, the offspring groups were separated by sex. It was observed that the consumption of FRU affected the food consumption, serum concentration of FRU, and glycemic profile in the mothers and that the VPE decreases these parameters. In addition, FRU was genotoxic in the mothers' peripheral tissues and VPE had a preventive effect on these parameters. The offspring showed changes in food consumption, serum FRU concentration, and body weight, in addition to an increase in the adiposity index in male offspring in the FRU (FRU) group and a decrease in the FRU + VPE group. FRU leads to hepatic steatosis in the offspring and VPE was able to decrease the area of steatosis. In addition, FRU led to genotoxicity in the offspring and VPE was able to modulate this effect, reducing damages. In conclusion, we observed that all interventions with VPE had nutritional, genetic, and biochemical benefits of the mother and her offspring.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138461105","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 : 2024-03-12DOI: 10.1093/mutage/gead038
Feng Zhao, Wenjuan Zhou, Ran Xin, Xin Miao
{"title":"Expression and clinical diagnostic value of CCHE1 in breast cancer.","authors":"Feng Zhao, Wenjuan Zhou, Ran Xin, Xin Miao","doi":"10.1093/mutage/gead038","DOIUrl":"10.1093/mutage/gead038","url":null,"abstract":"<p><strong>Objective: </strong>Breast cancer is a malignant tumor in the epithelial tissue of the breast gland. This study aimed to unveil the expression and clinical diagnostic value of lncRNA cervical cancer high-expressed 1 (CCHE1) in breast cancer.</p><p><strong>Methods: </strong>CCHE1 expression in breast cancer tissues was evaluated by RT-qPCR. The relationship between the CCHE1 expression and clinicopathological features of breast cancer was analyzed with the chi-square test, and the survival of breast cancer patients was evaluated with the Kaplan-Meier method. The diagnostic value of CCHE1 expression for breast cancer was evaluated by using the receiver operating characteristics (ROC) curve. Breast cancer cell lines (SKBR3, T47D, BT474, and MCF-7) were cultured for detecting CCHE1 expression in the cells. MCF-7 cells were selected for the subsequent experiments, and the small interfering RNA of CCHE1 (si-CCHE1) and CCHE1 overexpression vector (pcDNA-CCHE1) were transfected into MCF-7 cells. The proliferation, migration, and invasive ability were assessed by CCK-8 and Transwell assays. The influence of CCHE1 on the growth of tumors was validated by nude mice xenograft assay.</p><p><strong>Results: </strong>CCHE1 was up-regulated in breast cancer tissues and breast cancer cells. The high expression level of CCHE1 in cancer tissues of breast cancer patients was correlated with larger tumor size, advanced TNM stage, Ki-67 status, and lymph node metastasis. The area under the ROC curve for CCHE1 in the diagnosis of breast cancer was 0.983 (95% CI: 0.966-1.000), with a sensitivity of 95.00% and a specificity of 91.70%. The 5-year survival rate was higher in patients with low CCHE1 expression than those with high CCHE1 expression. Furthermore, restrained CCHE1 impeded proliferation, invasion, and migration of MCF-7 cells, as well as tumor growth in mice.</p><p><strong>Conclusion: </strong>Our study highlights that elevated expression of CCHE1 in breast cancer tissues, which is closely related to clinicopathologic features, has some clinical value in the diagnosis of the disease.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048995","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}