Food and Chemical Toxicology最新文献_第7页

The Alarming Consequences of Workforce Reductions at the FDA, EPA, NIH and CDC in the United States 美国FDA、EPA、NIH和CDC裁员的惊人后果

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2025-05-04 DOI: 10.1016/j.fct.2025.115510

Martin van den Berg PhD (Editor-in-Chief, Regulatory Toxicology & Pharmacology and Current Opinion in Toxicology) , Daniel R. Dietrich PhD (Editor-in-Chief, Chemico-Biological Interactions, Computational Toxicology, and Journal of Toxicology and Regulatory Policy) , Sonja von Aulock PhD (Editor-in-Chief, ALTEX –Alternatives to Animal Experimentation) , Anna Bal-Price PhD (Editor-in-Chief, Reproductive Toxicology) , Michael D. Coleman PhD (Editor-in-Chief, Environmental Toxicology and Pharmacology) , Mark T.D. Cronin PhD (Editor-in-Chief, Computational Toxicology) , Paul Jennings PhD (Editor-in-Chief, Toxicology in Vitro) , Angela Mally PhD (Editor-in-Chief, Toxicology Letters) , Mathieu Vinken PhD (Editor-in-Chief, Toxicology and NAM Journal) , Matthew C. Wright PhD (Editor-in-Chief, Food and Chemical Toxicology)

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RIFM Natural Complex Substance (NCS) fragrance ingredient safety assessment, savory winter oil, CAS Registry Number 90106-57-3, RIFM ID 1181-E2.12. 天然复合物质（NCS）香味成分安全性评估，香冬油，CAS注册号90106-57-3，RIFM ID 1181-E2.12。

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2025-05-03 DOI: 10.1016/j.fct.2025.115492

A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M Cronin, S Crotty, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, L Jones, K Joshi, A Lapczynski, D L Laskin, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar

{"title":"RIFM Natural Complex Substance (NCS) fragrance ingredient safety assessment, savory winter oil, CAS Registry Number 90106-57-3, RIFM ID 1181-E2.12.","authors":"A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M Cronin, S Crotty, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, L Jones, K Joshi, A Lapczynski, D L Laskin, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar","doi":"10.1016/j.fct.2025.115492","DOIUrl":"10.1016/j.fct.2025.115492","url":null,"abstract":"<p><p>Savory winter oil was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data for components of the NCS do not show a concern for genotoxicity. Savory winter oil was evaluated for the repeated dose and reproductive toxicity endpoints on the basis of component analysis using a combination of target data, read-across data, and the Threshold of Toxicological Concern (TTC); Savory winter oil is safe for use under the conditions described in this safety assessment for the repeated dose and reproductive toxicity endpoints. Data for components of the NCS do not show a concern for skin sensitization under the current, declared levels of use. The photoirritation endpoint was evaluated based on ultraviolet (UV/Vis) absorption spectra for the whole NCS; Savory winter oil is not expected to be photoirritating. The photoallergenicity endpoint was evaluated based on UV/Vis absorption spectra for the whole NCS. Savory winter oil is not expected to be photoallergenic. The local respiratory toxicity endpoint for this NCS was evaluated using the inhalation TTC for a Cramer Class III material, and the inhalation exposure to Savory winter oil is below the TTC (0.47 mg/day). Based on the component assessment, Savory winter oil does not contain PBT or vPvB components as per the IFRA Environmental Standards and does not present a risk to the aquatic environment at the current reported volumes of use.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115492"},"PeriodicalIF":3.9,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adsorption of dibutyl phthalate by multi-walled carbon nanotubes aggravates hemogram, liver and kidney damage in rats 多壁碳纳米管吸附邻苯二甲酸二丁酯可加重大鼠血象、肝脏和肾脏损伤

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2025-05-03 DOI: 10.1016/j.fct.2025.115499

Min Wu , Chao Yan , Haiyan Peng , Jian Wan , Ren Li , Xin Ye , Hongmao Zhang , Shumao Ding

引用次数: 0

FKBP51 protects hair cells of utricles from gentamicin-induced toxicity in vitro: possible relation to the activities of NF-κB signaling pathway FKBP51保护胞囊毛细胞免受庆大霉素诱导的体外毒性：可能与NF-κB信号通路活性有关

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2025-05-03 DOI: 10.1016/j.fct.2025.115513

Yanan Li , Ning Li , Junhong Zhang , Xueyan Liu , Yue Xu , Ligang Kong , Rongjun Man , Jianfeng Li

{"title":"FKBP51 protects hair cells of utricles from gentamicin-induced toxicity in vitro: possible relation to the activities of NF-κB signaling pathway","authors":"Yanan Li , Ning Li , Junhong Zhang , Xueyan Liu , Yue Xu , Ligang Kong , Rongjun Man , Jianfeng Li","doi":"10.1016/j.fct.2025.115513","DOIUrl":"10.1016/j.fct.2025.115513","url":null,"abstract":"<div><div>FK506-binding protein 51 (FKBP51) belongs to the immunophilin family, which is related to regulation of cell growth and apoptosis. The present study was designed to explore the expression of FKBP51 in murine utricle hair cells (HCs) and the possible mechanisms underpinning the actions of FKBP51 relevant to gentamicin-mediated toxicity, with special attention given to nuclear factor-kappa B (NF-κB) activities in vitro. Here, we found, for the first time, that FKBP51 was widely expressed in both cytoplasm and cytomembrane. Moreover, the expression of FKBP51 in cultured HCs of utricle was downregulated after exposure to 1 mM gentamicin for 24 h. Then, the <em>fkbp51</em> knockout mice were utilized to further investigate the role of FKBP51 in HCs in response to gentamicin. And the absence of FKBP51 led to severe HCs loss, accumulated ROS levels, and increased apoptotic factors, which could be alleviated by 2 mM N-acetyl-<span>l</span>-cysteine (NAC) to certain degree. In addition, mechanistic studies with 10 mM BAY 11–7082 showed that FKBP51 protected HCs against gentamicin-induced damage, at least in part, via blocking the NF-κB pathway activation. Taken together, our new findings suggest that FKBP51 might serve as a new target for the prevention of HCs of utricle from aminoglycoside-induced vestibular toxicity.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"202 ","pages":"Article 115513"},"PeriodicalIF":3.9,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assessment of mercury and selenium concentrations in Sepia pharaonis and Uroteuthis duvauceli from the Persian Gulf, Iran: Implications for human health and seafood safety 伊朗波斯湾法老蛤和杜沃塞利鱼中汞和硒浓度的评估：对人类健康和海产品安全的影响

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2025-05-03 DOI: 10.1016/j.fct.2025.115516

Reza Dahmardeh Behrooz , Sanaz Khammar , Reza Asvad , Abbas Esmaili-sari , Joanna Burger

{"title":"Assessment of mercury and selenium concentrations in Sepia pharaonis and Uroteuthis duvauceli from the Persian Gulf, Iran: Implications for human health and seafood safety","authors":"Reza Dahmardeh Behrooz , Sanaz Khammar , Reza Asvad , Abbas Esmaili-sari , Joanna Burger","doi":"10.1016/j.fct.2025.115516","DOIUrl":"10.1016/j.fct.2025.115516","url":null,"abstract":"<div><div>This study investigates the concentrations of mercury and selenium in <em>Sepia pharaonis</em> and <em>Uroteuthis duvauceli</em> from the Persian Gulf. Based on 30 sample from these species our results showed that the concentration of mercury and selenium metals in the hepatopancreas of both species was significantly higher than in the muscle, with <em>Uroteuthis duvauceli</em> exhibiting higher overall mercury concentrations than <em>Sepia pharaonis</em>. Selenium concentrations were lower than mercury concentrations. The correlation of mercury and selenium in muscle and hepatopancreas of <em>Sepia pharaonis</em> and <em>Uroteuthis duvauceli</em> was negative; the correlations was clearer for the hepatopancreas. Furthermore, the daily intake values and hazard indices calculated for both metals indicated that selenium poses minimal risk, while the consumption of these cephalopods warrants caution due to elevated mercury levels. The study emphasizes the importance of continued vigilance and species-specific assessments to ensure safe seafood consumption and protect public health.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"202 ","pages":"Article 115516"},"PeriodicalIF":3.9,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MEHP impairs male reproductive function through the lipid metabolism pathway: Evidence from in vitro human immature testis culture MEHP通过脂质代谢途径损害男性生殖功能：来自体外人类未成熟睾丸培养的证据

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2025-05-02 DOI: 10.1016/j.fct.2025.115502

Dinggang Li , Xia Wang , Jie Zhao , Xiangqin Zheng , Runchang Wang , Peng Zhao , Wei Deng , Mingxin Wang , Hao Yan , Lianju Shen , Yi Wei , Shengde Wu

{"title":"MEHP impairs male reproductive function through the lipid metabolism pathway: Evidence from in vitro human immature testis culture","authors":"Dinggang Li , Xia Wang , Jie Zhao , Xiangqin Zheng , Runchang Wang , Peng Zhao , Wei Deng , Mingxin Wang , Hao Yan , Lianju Shen , Yi Wei , Shengde Wu","doi":"10.1016/j.fct.2025.115502","DOIUrl":"10.1016/j.fct.2025.115502","url":null,"abstract":"<div><div>Di-(2-ethylhexyl) phthalate (DEHP) is a widely used industrial plasticizer whose main metabolite in the body is mono-(2-ethylhexyl) phthalate (MEHP). The reproductive toxicity of DEHP and MEHP has been documented in some studies. However, precise mechanisms remain unclear, and most research has focused on animal models. In this study, an <em>in vitro</em> culture system of immature human testicular tissue was employed to explore the etiological link between MEHP and developmental toxicity in immature human testes. The examination of micro-morphology, subcellular structure and testosterone secretion demonstrated that immature human testicular tissue could grow best at the temperature of 34 °C in this <em>in vitro</em> culture system. MEHP exposure damaged organelles, reduced testosterone secretion, disrupted oxidative stress and autophagy expression levels. Transcriptome sequencing revealed that differentially expressed genes (DEGs) were mainly associated with lipid metabolism pathways, which indicated the key role of DEGs in MEHP-induced reproductive toxicity. In the current study, the toxicological mechanisms of MEHP were investigated using an <em>in vitro</em> model of immature human testicular tissue. The lipid metabolism pathway could be a critical molecular pathway involved. This study offers a theoretical basis for understanding toxic damage from environmental toxins.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"202 ","pages":"Article 115502"},"PeriodicalIF":3.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring hidden natural resources for bioactive compounds: Focused chemical and biological studies on some Anthemis species 探索隐藏的天然生物活性化合物资源：对一些菊花种类的集中化学和生物学研究

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2025-05-02 DOI: 10.1016/j.fct.2025.115467

Dimitrina Zheleva-Dimitrova , Reneta Gevrenova , Sakina Yagi , Mehmet Veysi Cetiz , Evren Yildiztugay , Ilhami Gulcin , Ismail Yapici , Simonetta Cristina Di Simone , Giustino Orlando , Luigi Menghini , Claudio Ferrante , Annalisa Chiavaroli , Gokhan Zengin

{"title":"Exploring hidden natural resources for bioactive compounds: Focused chemical and biological studies on some Anthemis species","authors":"Dimitrina Zheleva-Dimitrova , Reneta Gevrenova , Sakina Yagi , Mehmet Veysi Cetiz , Evren Yildiztugay , Ilhami Gulcin , Ismail Yapici , Simonetta Cristina Di Simone , Giustino Orlando , Luigi Menghini , Claudio Ferrante , Annalisa Chiavaroli , Gokhan Zengin","doi":"10.1016/j.fct.2025.115467","DOIUrl":"10.1016/j.fct.2025.115467","url":null,"abstract":"<div><div>The present study investigated the phytochemical composition and biological activities of extracts from the aerial parts of <em>Anthemis austriaca, A. cretica</em> subsp. <em>albida, A. pauciloba, A. tinctoria</em> and <em>A. wiedemanniana.</em> About 150 compounds belonging to hydroxybenzoic acids, hydroxycinnamic acids, phenylethanoid glycosides, acylquinic acids, acylhexaric acids, flavonoids and sesquiterpene lactones were identified. <em>A</em>. <em>tinctoria</em> also displayed significant antiradical activity, obtained from its MeOH and 70 % MeOH extracts. EtOAc and MeOH extracts of <em>A. pauciloba</em> revealed the highest anti-acetylcholinesterase activity (3.51 and 3.50 mg GALAE/g; <em>p</em> > 0.05). Extracts had a higher affinity towards human carbonic anhydrase isoenzymes I (CAI) than CAII, and the best inhibition effect was exerted by EtOAc extract of <em>A. wiedemanniana a</em> (IC<sub>50</sub> 7.02 μg/mL). Network pharmacology analysis identified IL6 and TNFα as key targets of these plant-derived molecules, underscoring their multi-target potential. <em>Anthemis</em> extracts' efficacy in blunting LPS-induced IL6 and TNFα gene expression in isolated mouse colon has confirmed these predictions. Molecular docking studies further confirmed that these compounds interact with multiple transcription factors (TFs), suggesting broad pharmacological activity. These results indicated that the five <em>Anthemis</em> species could be a promising source of bioactive molecules.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"202 ","pages":"Article 115467"},"PeriodicalIF":3.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143911956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prenatal genistein exposure in rats affects pubertal onset and serum reproductive hormone levels in male offsprings via the hypothalamic-pituitary-gonadal axis 大鼠产前暴露染料木素通过下丘脑-垂体-性腺轴影响雄性后代的青春期发病和血清生殖激素水平

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2025-05-02 DOI: 10.1016/j.fct.2025.115498

Jing Zi , Guochen Ma , Yifan Hu , Xinlong Li , Qianqian Cao , Yanliu Li , Xiaoyu Wang , Guo Cheng , Jingyuan Xiong

{"title":"Prenatal genistein exposure in rats affects pubertal onset and serum reproductive hormone levels in male offsprings via the hypothalamic-pituitary-gonadal axis","authors":"Jing Zi , Guochen Ma , Yifan Hu , Xinlong Li , Qianqian Cao , Yanliu Li , Xiaoyu Wang , Guo Cheng , Jingyuan Xiong","doi":"10.1016/j.fct.2025.115498","DOIUrl":"10.1016/j.fct.2025.115498","url":null,"abstract":"<div><div>Genistein, an abundant phytoestrogen found in soy and soy products, can cross the placental barrier. However, impacts of prenatal genistein on male offspring reproductive development are unclear. Here, pregnant Sprague-Dawley rats were exposed to genistein at 1, 10, and 20 mg/kg·bw/day from gestational day 0–17. Medium- and high-dose prenatal genistein delayed pubertal onset in male offspring by 2–3 days, reduced body weight, increased the testis-to-body weight ratio and shortened anogenital distance. Testicular histology revealed disorganized seminiferous tubules and reduced germ cell numbers. At pubertal onset, serum levels of gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone and estradiol were increased in medium- and high-dose groups, while at postnatal day 49, serum level of testosterone was decreased. Real-Time quantitative PCR revealed reduced transcription of <em>Kiss1</em> and <em>Esr1</em>, and elevated transcription of <em>Gnrh1</em> in hypothalamus; reduced transcription of <em>Esr1</em>, <em>Gnrhr</em>, <em>Fshb</em> and <em>Lhb</em> in pituitary; and elevated transcription of <em>Esr2</em>, <em>Lhcgr</em>, <em>Cyp11a1</em> and <em>Inhba</em> in testes. Immunohistochemistry and Western-blot analyses showed dysregulated protein expression of KISS1, GnRHR, and FSHR. In conclusion, prenatal genistein exposure in rats delays pubertal onset in male offspring by affecting hypothalamic-pituitary-gonadal axis, highlighting potential transgenerational impacts of prenatal phytoestrogen on pubertal and reproductive development of male offspring.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"202 ","pages":"Article 115498"},"PeriodicalIF":3.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human health risk assessment of three smoke flavoring primary products 三种烟熏香精初级产品的人体健康风险评价

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2025-05-02 DOI: 10.1016/j.fct.2025.115490

G. Brorby , A. Franzen , C. Thompson , D. Wikoff , C. Doepker

{"title":"Human health risk assessment of three smoke flavoring primary products","authors":"G. Brorby , A. Franzen , C. Thompson , D. Wikoff , C. Doepker","doi":"10.1016/j.fct.2025.115490","DOIUrl":"10.1016/j.fct.2025.115490","url":null,"abstract":"<div><div>As part of a mandatory 10-year re-authorization process, the safety of three Smoke Flavoring Primary Products (SFPPs) was assessed based on EFSA's guidance. Data available for three SFPPs included OECD guideline studies for <em>in vivo</em> genotoxicity, reproductive/developmental screening, and subchronic toxicity. Genotoxicity potential of individual constituents (∼50/SFPP) was also evaluated using existing data identified systematically or via <em>in silico</em> methods as required by EFSA. No constituents were determined to pose a genotoxic risk under conditions of intended use. Whole mixture genotoxicity studies were negative at doses up to 7000 or 10,234 mg/kg-body weight/day in micronucleus and transgenic rodent assays, respectively, much higher than typical limit doses. Whole mixture reproductive/developmental screening and subchronic 90-day testing data were also negative. The lowest NOAELs were the highest doses tested in the subchronic studies (785-1367 mg/kg-body weight/day). Human exposure was conservatively assessed using multiple approaches; the most refined exposure estimates assuming typical SFPP use levels were derived using EFSA's DietEx model adjusted for market share (0.29–0.42 mg/kg-body weight/day). The resulting margins of safety (2000–4700) between the health benchmark and exposure estimates exceed EFSA's target of 300 for each SFPP, thus supporting continued use of these SFPPs as safe alternatives to conventional smoking of food.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"202 ","pages":"Article 115490"},"PeriodicalIF":3.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cr (VI) induces lactate utilization through HIF-1α/MCT1 dependent on p53 protein level Cr （VI）通过HIF-1α/MCT1诱导乳酸利用，依赖于p53蛋白水平

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2025-05-02 DOI: 10.1016/j.fct.2025.115505

Shengnan Li , Yajing Guo , Xiaojing Cui , Li Li , Jianhui Fan , Jun Cao

{"title":"Cr (VI) induces lactate utilization through HIF-1α/MCT1 dependent on p53 protein level","authors":"Shengnan Li , Yajing Guo , Xiaojing Cui , Li Li , Jianhui Fan , Jun Cao","doi":"10.1016/j.fct.2025.115505","DOIUrl":"10.1016/j.fct.2025.115505","url":null,"abstract":"<div><div>Hexavalent chromium [Cr (VI)] is a known environmental pollutant, which promotes tumorigenesis. Hypoxia-inducible factor-1α (HIF-1α) is crucial for cancer development. Here, we found that Cr (VI) treatment promoted lactate utilization by increasing monocarboxylate transporter 1 (MCT1) and monocarboxylate transporter 4 (MCT4) expression, while increasing the expression of HIF-1α in A549 cells but reducing HIF-1α and MCT1 in HELF cells. CoCl<sub>2</sub>, an HIF-1α inducer, increased MCT1, while the HIF-1α inhibitor YC-1 and MCT1 inhibitor AZD3965 suppressed Cr (VI)-induced lactate utilization and cell growth. Chromatin immunoprecipitation (ChIP) assay revealed HIF-1α bound to the MCT1 promoter to enhance its transcription. Using Reactivating p53 and Inducing Tumor Apoptosis (RITA), which can increase the protein level of p53, we discovered that the low level of p53 protein in A549 cells determined the effect of Cr (VI)-induced HIF-1α. These findings highlighted the role of p53 protein level in the effects of Cr (VI) on HIF-1α/MCT1 to induce lactate utilization and cell growth. Targeting the p53/HIF-1α/MCT1 pathway could inhibit Cr (VI)-mediated tumorigenesis.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"202 ","pages":"Article 115505"},"PeriodicalIF":3.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0