Pub Date : 2026-01-01Epub Date: 2025-12-17DOI: 10.1016/j.mrgentox.2025.503913
Kajal Gaur , Yasir Hasan Siddique
Bis(2-ethylhexyl) phthalate (DEHP) is a widely used synthetic compound known for its significant environmental and health hazards. It is particularly recognized for disrupting cellular functions by interfering with endocrine activity and inducing oxidative stress. Our previous research established that DEHP causes both cytotoxic and genotoxic effects in third instar larvae of Drosophila melanogaster (hsp70-lacZ) Bg9. The present study explores the protective role of apigenin, a naturally occurring flavonoid, against DEHP-induced toxicity in the model organism. Apigenin was mixed into the larval diet at concentrations of 20, 40, 60, and 80 µM, alongside 0.02 M DEHP, and administered for 24 h. Our findings revealed that apigenin supplementation significantly reduced gut tissue damage, lowered Hsp70 expression, and decreased both the apoptotic index and DNA damage in third instar larvae exposed to DEHP. Apigenin effectively reduced the elevated activities of caspase-3 and caspase-9 induced by Bis(2-ethylhexyl) phthalate exposure. These results highlight apigenin’s potential as an effective protective agent against the toxic effects of DEHP.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种广泛使用的合成化合物，因其对环境和健康有重大危害而闻名。它特别被认为是通过干扰内分泌活动和诱导氧化应激来破坏细胞功能。我们之前的研究证实DEHP对黑腹果蝇（Drosophila melanogaster, hsp70-lacZ） Bg9三龄幼虫具有细胞毒性和基因毒性作用。本研究探讨了芹菜素（一种天然存在的类黄酮）对模型生物中dehp诱导的毒性的保护作用。将芹菜素以20、40、60和80µM的浓度与0.02 M DEHP混合到幼虫饲料中，并给予24 h。我们的研究结果表明，添加芹菜素可以显著减少DEHP暴露的3龄幼虫的肠道组织损伤，降低Hsp70的表达，降低凋亡指数和DNA损伤。芹菜素有效降低了邻苯二甲酸双（2-乙基己基）暴露引起的caspase-3和caspase-9活性升高。这些结果突出了芹菜素作为抗DEHP毒性作用的有效保护剂的潜力。
{"title":"Effect of apigenin against Bis(2-ethylhexyl) phthalate induced toxicity on Drosophila melanogaster","authors":"Kajal Gaur , Yasir Hasan Siddique","doi":"10.1016/j.mrgentox.2025.503913","DOIUrl":"10.1016/j.mrgentox.2025.503913","url":null,"abstract":"<div><div>Bis(2-ethylhexyl) phthalate (DEHP) is a widely used synthetic compound known for its significant environmental and health hazards. It is particularly recognized for disrupting cellular functions by interfering with endocrine activity and inducing oxidative stress. Our previous research established that DEHP causes both cytotoxic and genotoxic effects in third instar larvae of <em>Drosophila melanogaster (hsp70-lacZ) Bg</em><sup><em>9</em></sup>. The present study explores the protective role of apigenin, a naturally occurring flavonoid, against DEHP-induced toxicity in the model organism. Apigenin was mixed into the larval diet at concentrations of 20, 40, 60, and 80 µM, alongside 0.02 M DEHP, and administered for 24 h. Our findings revealed that apigenin supplementation significantly reduced gut tissue damage, lowered Hsp70 expression, and decreased both the apoptotic index and DNA damage in third instar larvae exposed to DEHP. Apigenin effectively reduced the elevated activities of caspase-3 and caspase-9 induced by Bis(2-ethylhexyl) phthalate exposure. These results highlight apigenin’s potential as an effective protective agent against the toxic effects of DEHP.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"909 ","pages":"Article 503913"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788054","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}
Pub Date : 2026-01-01Epub Date: 2025-12-03DOI: 10.1016/j.mrgentox.2025.503904
Diene da Silva Schlickmann , Gabriela Cristina Uebel , Patrícia Molz , Nikolas Mateus Pereira de Souza , Renato Alberto Weber Colombelli , Aline Alves da Luz , Munithele Moraes Eisenhardt , Geovana Andrine Vogt , Caroline Brand , Eliane Aparecida de Castro , Pedro J. Benito , Alexandre Rieger , Silvia Isabel Rech Franke
This cross-sectional study evaluated dietary and lifestyle factors potentially contributing to DNA damage, cytokinetic defects, proliferative potential, and cell death among gym users in Brazil and Spain. We assessed demographic data, exercise habits, and nutrient estimated intake in 127 Brazilians and 101 Spaniards (≥18 years). DNA damage (micronuclei and/or nuclear buds), cytokinetic defects (binucleated cells), proliferative potential (normal cell frequency), and cell death (condensed chromatin, karyorrhexis, pyknotic, and karyolytic cells) were evaluated using the buccal micronucleus cytome assay (BMCyt). Multivariate analysis using partial least-squares discriminant analysis (PLS-DA) revealed significant discrimination between populations (AUC=0.976, sensitivity=90 %, specificity=95 %). Brazilians showed higher estimated carbohydrate consumption (220.9 vs 182.8 g/day, p = 0.001) and increased cell death markers, particularly karyorrhexis cells (p < 0.001; r = 0.94). Spaniards exhibited higher estimated intake of protein (121.1 vs 89.5 g/day), vitamins E and C, and manganese (all p < 0.001), with lower cellular damage frequencies. Results suggest a higher estimated intake of dietary antioxidants may provide protective effects against cytotoxic damage in different cultural contexts.
{"title":"Genotoxic and cytotoxic effects of dietary patterns and lifestyle factors: A cross-sectional comparison of Brazilian and Spanish gym users","authors":"Diene da Silva Schlickmann , Gabriela Cristina Uebel , Patrícia Molz , Nikolas Mateus Pereira de Souza , Renato Alberto Weber Colombelli , Aline Alves da Luz , Munithele Moraes Eisenhardt , Geovana Andrine Vogt , Caroline Brand , Eliane Aparecida de Castro , Pedro J. Benito , Alexandre Rieger , Silvia Isabel Rech Franke","doi":"10.1016/j.mrgentox.2025.503904","DOIUrl":"10.1016/j.mrgentox.2025.503904","url":null,"abstract":"<div><div>This cross-sectional study evaluated dietary and lifestyle factors potentially contributing to DNA damage, cytokinetic defects, proliferative potential, and cell death among gym users in Brazil and Spain. We assessed demographic data, exercise habits, and nutrient estimated intake in 127 Brazilians and 101 Spaniards (≥18 years). DNA damage (micronuclei and/or nuclear buds), cytokinetic defects (binucleated cells), proliferative potential (normal cell frequency), and cell death (condensed chromatin, karyorrhexis, pyknotic, and karyolytic cells) were evaluated using the buccal micronucleus cytome assay (BMCyt). Multivariate analysis using partial least-squares discriminant analysis (PLS-DA) revealed significant discrimination between populations (AUC=0.976, sensitivity=90 %, specificity=95 %). Brazilians showed higher estimated carbohydrate consumption (220.9 vs 182.8 g/day, p = 0.001) and increased cell death markers, particularly karyorrhexis cells (p < 0.001; r = 0.94). Spaniards exhibited higher estimated intake of protein (121.1 vs 89.5 g/day), vitamins E and C, and manganese (all p < 0.001), with lower cellular damage frequencies. Results suggest a higher estimated intake of dietary antioxidants may provide protective effects against cytotoxic damage in different cultural contexts.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"909 ","pages":"Article 503904"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145683681","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}
Pub Date : 2026-01-01Epub Date: 2025-12-13DOI: 10.1016/j.mrgentox.2025.503912
Ana María Palermo, Eliana Ruth Steinberg, Marta Dolores Mudry
Methanol (MeOH) is a colorless, flammable, poisonous, alcohol that causes intoxication by ingesting, inhaling or by contact with formulations that include it. It is produced in large volumes and there is high level of human exposure, especially by the inhalation route. It has been reported as innocuous in various test systems; thus, the aim of this work was to search for in vivo genotoxic effects of MeOH in Drosophila melanogaster, studying its ability to induce nondisjunction (ND) in females. Treatments were acute (60 min) and via inhalation. It was toxic in 1-day old flies (MI = 63 % for 75 % MeOH) and in 5-days old flies (MI = 8.4 %, 40 % MeOH). Female fertility was severely affected during the first 24 h after treatment, later control values were recovered. MeOH induced a 16-fold increase of ND (%) in 1-day old females, and a 9-fold rise in 5-days old female’s offspring, but control values were recovered in the offspring of subsequent broods. These findings suggest that the main effect of MeOH is to induce chromosomal malsegregation when present at the resumption of M-phase I after fertilization, probably due to perturbations in the nuclear membrane. Therefore, negative results with assays that evaluate DNA damage do not imply that the compound tested is not a potential hazard because other cellular components could be modified.
{"title":"Chromosome malsegregation induced by methanol in Drosophila melanogaster females","authors":"Ana María Palermo, Eliana Ruth Steinberg, Marta Dolores Mudry","doi":"10.1016/j.mrgentox.2025.503912","DOIUrl":"10.1016/j.mrgentox.2025.503912","url":null,"abstract":"<div><div>Methanol (MeOH) is a colorless, flammable, poisonous, alcohol that causes intoxication by ingesting, inhaling or by contact with formulations that include it. It is produced in large volumes and there is high level of human exposure, especially by the inhalation route. It has been reported as innocuous in various test systems; thus, the aim of this work was to search for <em>in vivo</em> genotoxic effects of MeOH in <em>Drosophila melanogaster</em>, studying its ability to induce nondisjunction (ND) in females. Treatments were acute (60 min) and via inhalation. It was toxic in 1-day old flies (<em>MI</em> = 63 % for 75 % MeOH) and in 5-days old flies (<em>MI</em> = 8.4 %, 40 % MeOH). Female fertility was severely affected during the first 24 h after treatment, later control values were recovered. MeOH induced a 16-fold increase of ND (%) in 1-day old females, and a 9-fold rise in 5-days old female’s offspring, but control values were recovered in the offspring of subsequent broods. These findings suggest that the main effect of MeOH is to induce chromosomal malsegregation when present at the resumption of M-phase I after fertilization, probably due to perturbations in the nuclear membrane. Therefore, negative results with assays that evaluate DNA damage do not imply that the compound tested is not a potential hazard because other cellular components could be modified.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"909 ","pages":"Article 503912"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788055","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}
Pub Date : 2025-11-01Epub Date: 2025-11-27DOI: 10.1016/j.mrgentox.2025.503903
Keya Katare , Rohit Shetty , Arkasubhra Ghosh
Retinoblastoma (RB) is the most common pediatric ocular malignancy resulting from biallelic inactivation of the RB1 gene and can be fatal if not treated. With advances in chemotherapy and earlier diagnosis, the mortality rates in developed nations such as USA, Europe and Canada, have reduced to 3–5 %. Subsequently, the clinical focus has shifted to preserving visual acuity in these countries, whereas in developing nations, mortality rates still range from 40 % to 70 %. In India, about 70 % of the children presenting with RB in the clinic have already progressed to category D or E tumors. Since chemotherapy is still a mainstay of RB treatment, bystander toxicity remains an important concern. Although enucleation is necessary in 40–60 % of the RB cases, prior chemotherapy is still administered in most cases to debulk the tumors. As the majority of drugs used in chemotherapy employ DNA damaging agents, the review attempts to summarize the current knowledge regarding dysregulated DNA damage repair (DDR) genes in RB. Loss of the RB1 gene causes not only unrestricted cell cycle progression and cell division, driven by the E2F transcription factor family, but also leads to the accumulation of various other mutations and chromosomal aberrations, which may have a specific impact on the patients’ response to chemotherapy. Therefore, developing a more detailed perspective on the RB tumor DNA damage repair pathways is the focus of this review. Crystallizing the available information, we also propose the use of a few DDR inhibitors of the identified deregulated genes in retinoblastoma that are currently in clinical trials for other cancer types, as adjunct therapy to increase chemosensitivity of RB tumors and reduce chemotherapy-induced toxicity for better treatment outcomes.
{"title":"The potential implications of dysregulated DNA damage repair genes and their modulators as adjuvants for current chemotherapy regimens in Retinoblastoma tumors","authors":"Keya Katare , Rohit Shetty , Arkasubhra Ghosh","doi":"10.1016/j.mrgentox.2025.503903","DOIUrl":"10.1016/j.mrgentox.2025.503903","url":null,"abstract":"<div><div>Retinoblastoma (RB) is the most common pediatric ocular malignancy resulting from biallelic inactivation of the RB1 gene and can be fatal if not treated. With advances in chemotherapy and earlier diagnosis, the mortality rates in developed nations such as USA, Europe and Canada, have reduced to 3–5 %. Subsequently, the clinical focus has shifted to preserving visual acuity in these countries, whereas in developing nations, mortality rates still range from 40 % to 70 %. In India, about 70 % of the children presenting with RB in the clinic have already progressed to category D or E tumors. Since chemotherapy is still a mainstay of RB treatment, bystander toxicity remains an important concern. Although enucleation is necessary in 40–60 % of the RB cases, prior chemotherapy is still administered in most cases to debulk the tumors. As the majority of drugs used in chemotherapy employ DNA damaging agents, the review attempts to summarize the current knowledge regarding dysregulated DNA damage repair (DDR) genes in RB. Loss of the RB1 gene causes not only unrestricted cell cycle progression and cell division, driven by the E2F transcription factor family, but also leads to the accumulation of various other mutations and chromosomal aberrations, which may have a specific impact on the patients’ response to chemotherapy. Therefore, developing a more detailed perspective on the RB tumor DNA damage repair pathways is the focus of this review. Crystallizing the available information, we also propose the use of a few DDR inhibitors of the identified deregulated genes in retinoblastoma that are currently in clinical trials for other cancer types, as adjunct therapy to increase chemosensitivity of RB tumors and reduce chemotherapy-induced toxicity for better treatment outcomes.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"908 ","pages":"Article 503903"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681130","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}
Pub Date : 2025-11-01Epub Date: 2025-10-31DOI: 10.1016/j.mrgentox.2025.503901
Samit B. Kadam , MR Mayookh , N. Bhumika , Satendra Singh , Aditya Hazare , Rohini Karnat
We review the results of the ‘Enhanced’ Ames Test (EAT) for assessment of the mutagenicity of N-nitrosamines, integrating the data from six key studies. High (>98 %) purities of the nitrosamines were confirmed by LC-MS and glutathione co-incubation to avoid false-positive results. The most sensitive strains were Salmonella typhimurium TA1535 and Escherichia coli WP2 uvrA (pKM101), which detect primarily GC→AT transitions, typically induced by O6-alkylguanine DNA adducts. Strain TA100 gave variable responses and strains TA98 and TA1537 gave negative results. Bioactivation by hamster liver S9 (particularly at the 30 % v/v level), rich in cytochrome P450 (CYP) forms 2E1 and 2C19, was more effective than rat liver S9. N-Methyl-2-pyrrolidone and ethyl acetate inhibited metabolic activation but DMSO (up to 1.6 % v/v) and water did not. These findings support the use of a tiered EAT strategy with TA1535, WP2 uvrA, hamster S9, and validated solvents, in agreement with published guidelines, for the robust risk assessment of nitrosamine mutagenicity.
{"title":"Mutagenicity of nitrosamines in enhanced Ames tests: A review of strain, metabolism, and solvent effects","authors":"Samit B. Kadam , MR Mayookh , N. Bhumika , Satendra Singh , Aditya Hazare , Rohini Karnat","doi":"10.1016/j.mrgentox.2025.503901","DOIUrl":"10.1016/j.mrgentox.2025.503901","url":null,"abstract":"<div><div>We review the results of the ‘Enhanced’ Ames Test (EAT) for assessment of the mutagenicity of N-nitrosamines, integrating the data from six key studies. High (>98 %) purities of the nitrosamines were confirmed by LC-MS and glutathione co-incubation to avoid false-positive results. The most sensitive strains were <em>Salmonella typhimurium</em> TA1535 and <em>Escherichia coli</em> WP2 <em>uvr</em>A (pKM101), which detect primarily GC→AT transitions, typically induced by O<sup>6</sup>-alkylguanine DNA adducts. Strain TA100 gave variable responses and strains TA98 and TA1537 gave negative results. Bioactivation by hamster liver S9 (particularly at the 30 % v/v level), rich in cytochrome P450 (CYP) forms 2E1 and 2C19, was more effective than rat liver S9. <em>N</em>-Methyl-2-pyrrolidone and ethyl acetate inhibited metabolic activation but DMSO (up to 1.6 % v/v) and water did not. These findings support the use of a tiered EAT strategy with TA1535, WP2 <em>uvrA</em>, hamster S9, and validated solvents, in agreement with published guidelines, for the robust risk assessment of nitrosamine mutagenicity.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"908 ","pages":"Article 503901"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145428595","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}
Pub Date : 2025-11-01Epub Date: 2025-11-06DOI: 10.1016/j.mrgentox.2025.503902
Makoto Hayashi , Takashi Omori
The appropriate strategy for a genotoxicity assessment depends on the purpose of the study. If the purpose is research-oriented (for example, to understand mechanisms of gene-mutation events or chromosomal aberrations), the tests should meet the researcher’s scientific goals. However, to make regulatory decisions with confidence, the genotoxicity strategy must cover all necessary endpoints. Thus, it is crucial to standardize the relevant test methods and to certify reproducible experimental processes. A battery system, which is often used for genotoxicity evaluation, consists of several tests that complementarily detect different endpoints. Numerous genotoxicity tests are available, employing various organisms and methodologies, and it is therefore crucial to select the appropriate tests for the battery system. Sensitivity and specificity are essential considerations. These are inversely correlated, and we cannot maximize them simultaneously; our interest tends to lie more with sensitivity than specificity; that is, we want to avoid false negatives. We also discuss the issues arising in parallel from a statistical perspective, namely type I and II errors. Genotoxicity is a crucial endpoint for decision-making in human safety assessment, and the issues mentioned above must be thoroughly understood and considered.
{"title":"Selection of tests for genotoxicity assessment: Sensitivity and specificity considerations","authors":"Makoto Hayashi , Takashi Omori","doi":"10.1016/j.mrgentox.2025.503902","DOIUrl":"10.1016/j.mrgentox.2025.503902","url":null,"abstract":"<div><div>The appropriate strategy for a genotoxicity assessment depends on the purpose of the study. If the purpose is research-oriented (for example, to understand mechanisms of gene-mutation events or chromosomal aberrations), the tests should meet the researcher’s scientific goals. However, to make regulatory decisions with confidence, the genotoxicity strategy must cover all necessary endpoints. Thus, it is crucial to standardize the relevant test methods and to certify reproducible experimental processes. A battery system, which is often used for genotoxicity evaluation, consists of several tests that complementarily detect different endpoints. Numerous genotoxicity tests are available, employing various organisms and methodologies, and it is therefore crucial to select the appropriate tests for the battery system. Sensitivity and specificity are essential considerations. These are inversely correlated, and we cannot maximize them simultaneously; our interest tends to lie more with sensitivity than specificity; that is, we want to avoid false negatives. We also discuss the issues arising in parallel from a statistical perspective, namely type I and II errors. Genotoxicity is a crucial endpoint for decision-making in human safety assessment, and the issues mentioned above must be thoroughly understood and considered.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"908 ","pages":"Article 503902"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733205","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}
Pub Date : 2025-10-01Epub Date: 2025-08-30DOI: 10.1016/j.mrgentox.2025.503885
Chuncao He , Xueying Sun , Ting Xu , Xiaoqiang Hu , Jinyi Han , Kexin Xu , Qin Song , Ting Duan , Jun Yang
Oxidative stress is a major factor for aging. Nicotinamide mononucleotide (NMN) is a naturally occurring bioactive nucleotide and a precursor for nicotinamide adenine dinucleotide (NAD+), and accumulating evidences have shown that NMN is a promising anti-aging agent, however, the underlying molecular mechanisms remain to be elucidated. Therefore, in the current study, the protective effects of NMN on oxidative stress-induced damage to cells, in particular, the various types of cell death induced by oxidative stress, were evaluated. It was found that NMN inhibited hydrogen peroxide (H2O2)-induced decrease in A549 cell viability·H2O2-triggered reactive oxygen species (ROS) production was also diminished by NMN. Furthermore, results from 8-hydoxy 2 deoxyguanosine (8-OHdG) level, alkaline comet assay, and γ-H2AX foci formation indicated that NMN protected cells from H2O2-induced DNA damage. Detailed cell death analysis revealed that H2O2 caused A549 cell death mainly through apoptosis and ferroptosis, but not necroptosis or parthanatos, and NMN could effectively inhibit the apoptosis and ferroptosis pathways, thus protected cells from H2O2-induced cell death. Finally, we validated NMN protected against H2O2-induced organismal senescence in C. elegans. Taken together, these results suggests that NMN is a potent agent against oxidative stress, which could contribute to its anti-aging effects.
{"title":"Protective effects of nicotinamide mononucleotide on DNA damage and cell death in A549 cells and aging in C. elegans caused by hydrogen peroxide","authors":"Chuncao He , Xueying Sun , Ting Xu , Xiaoqiang Hu , Jinyi Han , Kexin Xu , Qin Song , Ting Duan , Jun Yang","doi":"10.1016/j.mrgentox.2025.503885","DOIUrl":"10.1016/j.mrgentox.2025.503885","url":null,"abstract":"<div><div>Oxidative stress is a major factor for aging. Nicotinamide mononucleotide (NMN) is a naturally occurring bioactive nucleotide and a precursor for nicotinamide adenine dinucleotide (NAD<sup>+</sup>), and accumulating evidences have shown that NMN is a promising anti-aging agent, however, the underlying molecular mechanisms remain to be elucidated. Therefore, in the current study, the protective effects of NMN on oxidative stress-induced damage to cells, in particular, the various types of cell death induced by oxidative stress, were evaluated. It was found that NMN inhibited hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-induced decrease in A549 cell viability·H<sub>2</sub>O<sub>2</sub>-triggered reactive oxygen species (ROS) production was also diminished by NMN. Furthermore, results from 8-hydoxy 2 deoxyguanosine (8-OHdG) level, alkaline comet assay, and γ-H2AX foci formation indicated that NMN protected cells from H<sub>2</sub>O<sub>2</sub>-induced DNA damage. Detailed cell death analysis revealed that H<sub>2</sub>O<sub>2</sub> caused A549 cell death mainly through apoptosis and ferroptosis, but not necroptosis or parthanatos, and NMN could effectively inhibit the apoptosis and ferroptosis pathways, thus protected cells from H<sub>2</sub>O<sub>2</sub>-induced cell death. Finally, we validated NMN protected against H<sub>2</sub>O<sub>2</sub>-induced organismal senescence in <em>C. elegans</em>. Taken together, these results suggests that NMN is a potent agent against oxidative stress, which could contribute to its anti-aging effects.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"Article 503885"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018927","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}
Cockayne Syndrome (CS), a progeroid disorder characterised by premature ageing and neurodevelopmental abnormalities, is primarily caused by mutations in the CSB protein, a key component of the transcription-coupled nucleotide excision repair pathway. This study investigates the role of CSB in managing oxidative DNA damage and preserving telomere integrity under oxidative stress. Using CSB-deficient human fibroblasts (CS-B) and matched controls, we exposed cells to acute and chronic oxidative stress via hydrogen peroxide (H₂O₂) and elevated oxygen (40 %) levels. CS-B fibroblasts showed relative resistance to acute oxidative stress in terms of cell death, maintaining viability and displaying limited cell cycle arrest. In contrast, chronic oxidative exposure induced accelerated senescence in CS-B cells, evidenced by increased telomere attrition, senescent morphology, and early activation of senescence-associated β-galactosidase associated with increased DNA damage and aberrant DNA repair. Gene expression profiling revealed downregulation of key DNA repair and cell cycle genes in CS-B fibroblasts following H₂O₂ treatment, indicating impaired damage response pathways. These findings highlight the essential role of CSB in genome maintenance and suggest that its loss contributes to CS pathology through heightened sensitivity to chronic oxidative stress and telomere dysfunction. This work enhances our understanding of CS-related cellular mechanisms and may inform future therapeutic strategies targeting oxidative stress and DNA repair.
{"title":"Protective role of Cockayne Syndrome B (CSB) protein in maintaining genome integrity in human cells under oxidative stress","authors":"Grace Kah Mun Low, Gavin Yong-Quan Ng, Dimphy Zeegers, Aloysius Ting, Kalpana Gopalakrishnan, Aik Kia Khaw, Manikandan Jayapal, Manoor Prakash Hande","doi":"10.1016/j.mrgentox.2025.503887","DOIUrl":"10.1016/j.mrgentox.2025.503887","url":null,"abstract":"<div><div>Cockayne Syndrome (CS), a progeroid disorder characterised by premature ageing and neurodevelopmental abnormalities, is primarily caused by mutations in the CSB protein, a key component of the transcription-coupled nucleotide excision repair pathway. This study investigates the role of CSB in managing oxidative DNA damage and preserving telomere integrity under oxidative stress. Using CSB-deficient human fibroblasts (CS-B) and matched controls, we exposed cells to acute and chronic oxidative stress via hydrogen peroxide (H₂O₂) and elevated oxygen (40 %) levels. CS-B fibroblasts showed relative resistance to acute oxidative stress in terms of cell death, maintaining viability and displaying limited cell cycle arrest. In contrast, chronic oxidative exposure induced accelerated senescence in CS-B cells, evidenced by increased telomere attrition, senescent morphology, and early activation of senescence-associated β-galactosidase associated with increased DNA damage and aberrant DNA repair. Gene expression profiling revealed downregulation of key DNA repair and cell cycle genes in CS-B fibroblasts following H₂O₂ treatment, indicating impaired damage response pathways. These findings highlight the essential role of CSB in genome maintenance and suggest that its loss contributes to CS pathology through heightened sensitivity to chronic oxidative stress and telomere dysfunction. This work enhances our understanding of CS-related cellular mechanisms and may inform future therapeutic strategies targeting oxidative stress and DNA repair.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"Article 503887"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145060561","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}
Pub Date : 2025-10-01Epub Date: 2025-08-26DOI: 10.1016/j.mrgentox.2025.503884
Tülay Aşkın Çelik , Ümit Ünsal
Perchloroethylene (PCE), a widely used solvent, is classified as a probable human carcinogen. We have studied its genotoxicity, clastogenicity, and cytotoxicity in cultured human peripheral lymphocytes (HPLs). Cytogenetic tests used were the chromosomal aberration (CA), sister chromatid exchange (SCE), mitotic index (MI), replication index (RI), and micronucleus (MN) assays. Positive results were obtained with each of these assays: a dose-dependent increase in CA, a significant increase in SCE, a significant decrease in MI and RI, and an increase in MN frequency at the highest concentration of PCE. These results demonstrate that PCE induces significant genotoxic and clastogenic effects in human peripheral lymphocytes.
{"title":"Perchloroethylene: Genotoxicity and cytotoxicity in human peripheral blood lymphocytes in vitro","authors":"Tülay Aşkın Çelik , Ümit Ünsal","doi":"10.1016/j.mrgentox.2025.503884","DOIUrl":"10.1016/j.mrgentox.2025.503884","url":null,"abstract":"<div><div>Perchloroethylene (PCE), a widely used solvent, is classified as a probable human carcinogen. We have studied its genotoxicity, clastogenicity, and cytotoxicity in cultured human peripheral lymphocytes (HPLs). Cytogenetic tests used were the chromosomal aberration (CA), sister chromatid exchange (SCE), mitotic index (MI), replication index (RI), and micronucleus (MN) assays. Positive results were obtained with each of these assays: a dose-dependent increase in CA, a significant increase in SCE, a significant decrease in MI and RI, and an increase in MN frequency at the highest concentration of PCE. These results demonstrate that PCE induces significant genotoxic and clastogenic effects in human peripheral lymphocytes.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"Article 503884"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932563","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}
Pub Date : 2025-10-01Epub Date: 2025-09-18DOI: 10.1016/j.mrgentox.2025.503897
Divya K. Mohan , Nandhini K. , Aishwarya S. , Senthil Kumar M. , Swetha K. , Akshaya J. , Sudha Pattan , Venkata Sai P.M. , Venkateswarlu Raavi , Venkatachalam Perumal
Computed tomography (CT) is a widely used diagnostic imaging modality that contributes significantly to human healthcare. Despite the advantage, its extensive use increased concerns due to receiving radiation doses to pediatric patient's over adults during CT imaging. We evaluated the biological effects (Gamma-H2AX (γ-H2AX) foci and micronucleus (MN) formation) of low-dose X-radiation on the peripheral blood lymphocytes of pediatric (n = 45) and adult (n = 38) participants before and after CT imaging. Participant-specific organ doses were calculated using VirtualDose™CT software, weighted to the corresponding organ's blood volume, summed to derive the blood dose, and then related to induced DNA damage. A significant (p < 0.001) increase in γ-H2AX foci and MN frequencies was observed in both pediatric and adult groups after CT imaging. While the mean effective dose (ED) in pediatric and adult (16.21 ± 11.33 mSv and 31.30 ± 16.25 mSv) participants were significantly different (p < 0.001), the mean blood doses did not differ (9.83 ± 6.34 mGy and 12.82 ± 5.96 mGy) (p > 0.05), respectively. A weak correlation was observed between the induced DNA damage to that of ED and blood dose. The results suggest that damage to blood lymphocytes after CT imaging was observed by an increased γ-H2AX foci result of DNA double-strand breaks. The increase in MN frequency suggests activation of DNA repair, thereby contributing to minimal damage, although they are unstable. Therefore, it is necessary to follow up on the pediatric participants to look for stable aberrations to better relate DNA damage to exposure and long-term health effects, if any.
{"title":"Frequency of γ-H2AX foci, micronucleus formation, and radiation dose to the blood lymphocytes in pediatric and adult participants underwent computed tomography imaging","authors":"Divya K. Mohan , Nandhini K. , Aishwarya S. , Senthil Kumar M. , Swetha K. , Akshaya J. , Sudha Pattan , Venkata Sai P.M. , Venkateswarlu Raavi , Venkatachalam Perumal","doi":"10.1016/j.mrgentox.2025.503897","DOIUrl":"10.1016/j.mrgentox.2025.503897","url":null,"abstract":"<div><div>Computed tomography (CT) is a widely used diagnostic imaging modality that contributes significantly to human healthcare. Despite the advantage, its extensive use increased concerns due to receiving radiation doses to pediatric patient's over adults during CT imaging. We evaluated the biological effects (Gamma-H2AX (γ-H2AX) foci and micronucleus (MN) formation) of low-dose X-radiation on the peripheral blood lymphocytes of pediatric (n = 45) and adult (n = 38) participants before and after CT imaging. Participant-specific organ doses were calculated using VirtualDose™CT software, weighted to the corresponding organ's blood volume, summed to derive the blood dose, and then related to induced DNA damage. A significant (p < 0.001) increase in γ-H2AX foci and MN frequencies was observed in both pediatric and adult groups after CT imaging. While the mean effective dose (ED) in pediatric and adult (16.21 ± 11.33 mSv and 31.30 ± 16.25 mSv) participants were significantly different (p < 0.001), the mean blood doses did not differ (9.83 ± 6.34 mGy and 12.82 ± 5.96 mGy) (p > 0.05), respectively. A weak correlation was observed between the induced DNA damage to that of ED and blood dose. The results suggest that damage to blood lymphocytes after CT imaging was observed by an increased γ-H2AX foci result of DNA double-strand breaks. The increase in MN frequency suggests activation of DNA repair, thereby contributing to minimal damage, although they are unstable. Therefore, it is necessary to follow up on the pediatric participants to look for stable aberrations to better relate DNA damage to exposure and long-term health effects, if any.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"Article 503897"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154355","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号