Toxicology Mechanisms and Methods最新文献

{"title":"Mechanistic paradigms of immunotoxicity, triggered by nanoparticles - a review.","authors":"S V S Rana","doi":"10.1080/15376516.2024.2431687","DOIUrl":"https://doi.org/10.1080/15376516.2024.2431687","url":null,"abstract":"<p><p>Nanoparticles (NPs) possess the ability to penetrate cells and elicit a rapid and targeted immune response, influenced by their distinct physicochemical properties. These particles can engage with both micro and macromolecules, thereby impacting various downstream signaling pathways that may lead to cell death. This review provides a comprehensive overview of the primary mechanisms contributing to the immunotoxicity of both organic and inorganic nanoparticles. The effects of carbon-based nanomaterials (CNMs), including single-walled carbon nanotubes, multi-walled carbon nanotubes, graphene, and metal oxide nanoparticles, on various immune cell types such as macrophages, neutrophils, monocytes, dendritic cells (DCs), antigen-presenting cells (APCs), and RAW 264.7 cells are examined. The immune responses discussed encompass inflammation, oxidative stress, autophagy, and apoptosis. Additionally, the roles of pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α, and IFN-γ, along with JAK/STAT signaling pathways, are highlighted. The interaction of NPs with oxidative stress pathways, including MAPK signaling and Nrf2/ARE signaling, is also explored. Furthermore, the mechanisms by which nanoparticles induce damage to organelles such as lysosomes, the endoplasmic reticulum, exosomes, and Golgi bodies within the immune system are addressed. The review also emphasizes the genotoxic and epigenetic mechanisms associated with the immunotoxicity of NPs. Recent advancements regarding the immunotherapeutic potential of engineered NPs are reported. The roles of autophagy and apoptosis in the immunotoxicity of NPs merit further investigation. In conclusion, understanding how engineered nanoparticles modulate immune responses may facilitate the prevention and treatment of human diseases, including cancer and autoimmune disorders. The potential development of new vaccines utilizing engineered NPs could pave the way for innovative approaches in the field of immunotherapy.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-29"},"PeriodicalIF":3.2,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711129","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":"From historical drugs to present perils: UHPLC-QqQ-MS/MS determination of methaqualone and its designer analogs (NPS) with comprehensive fragmentation pathways study (QTOF).","authors":"Kaja Tusiewicz, Olga Wachełko, Paweł Szpot, Marcin Zawadzki","doi":"10.1080/15376516.2024.2426582","DOIUrl":"10.1080/15376516.2024.2426582","url":null,"abstract":"<p><p>Methaqualone, introduced in the 1960s as a sedative-hypnotic alternative to barbiturates, was withdrawn from the market due to its side effects and growing recreational use. Despite this, interest in methaqualone and its analogs remains high, raising concerns about potential abuse in the future. An ultra-high-performance liquid chromatography method coupled with triple quadrupole tandem mass spectrometry (UHPLC-QqQ-MS/MS) was developed to determine nine methaqualone-related compounds simultaneously. Biological samples were prepared using liquid-liquid extraction with ethyl acetate at pH9; quantification was performed in blood using multiple reaction monitoring (MRM) mode. Methaqualone-<i>d₇</i> served as an internal standard. The limit of quantification (LOQ) ranged from 0.1 to 0.2 ng/mL, with precision and accuracy within 20%. Recovery ranged from 84.2% to 113.7%. The developed method allowed chromatographic separation of all compounds tested, including two structural isomers: methylmethaqualone and etaqualone. The mass spectra acquired from quadrupole time-of-flight mass spectrometer allowed for the elucidation of comprehensive fragmentation study of methaqualone derivatives. The described situation poses a significant problem from the analytical point of view, as well as interpretation and forensic toxicological expertise. The developed method will contribute to increased analytical capabilities and enhanced detection of compounds from the methaqualone group that may appear on the illicit market.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-11"},"PeriodicalIF":3.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606038","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":"Disposable electronic cigarettes - chemical composition and health effects of their use. A systematic review.","authors":"Paulina Natalia Kopa-Stojak, Rafal Pawliczak","doi":"10.1080/15376516.2024.2423927","DOIUrl":"https://doi.org/10.1080/15376516.2024.2423927","url":null,"abstract":"<p><strong>Objective: </strong>Despite the rising popularity of disposable e-cigarettes, little is known about their chemical characteristics, or their impact on users' health. This work attempts to summarize current knowledge about chemical composition and known health effects of disposable e-cigarettes.</p><p><strong>Methods: </strong>The literature search was performed in February and March 2024 in Pub Med and Science Direct databases (no time range) by the terms 'disposable electronic cigarette', 'disposable e-cigarette', 'disposable e-cigs', 'cig-a-like e-cigarette', 'cig-a-like electronic cigarette'.</p><p><strong>Results: </strong>Disposable e-cigarettes contain: nicotine, humectants (propylene glycol, glycerin), flavoring agents (diacetyl, acetoin, triacetin, p-menthone, triethyl citrate, ethyl maltol, 3-hexen-1-ol, methyl anthranilate, α-terpineol, perillartine, benzyl alcohol, vanillin, melonal, methyl dihydrojasmonate, and γ-decalactone), cooling agents (WS-3, WS-23, menthol), carbonyl compounds (acetaldehyde, formaldehyde, propionaldehyde, acetone, acrolein) volatile organic compounds (VOCs) (benzene, ethanol, methanol, styrene, acetylpirazine and 2,3,5-trimethylpyrazine), metals and inorganic compounds (chromium, nickel, manganese, lead, aluminum, and zinc) and reactive oxygen species. Furthermore, there was some evidence of nicotine dependence, risk of cancer and adverse respiratory effects of using disposable e-cigarettes.</p><p><strong>Conclusions: </strong>Despite the fact that disposable e-cigarettes contain significantly less toxins compared to combustible cigarettes, they include compounds that are absent in such products that may provide health risk in prolonged usage. In addition, there is a limited number of data on the health effect of disposable e-cigarettes, especially in long time period, for never-smokers. Therefore, due to growing popularity of disposable e-cigarettes among young people, who choose them when initiating nicotine use, further research on their long-term impact of on the users' health is necessary.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-12"},"PeriodicalIF":3.2,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606116","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":"Decoding the possible mechanism of action of Paeoniflorigenone in combating Aflatoxin B1-induced liver cancer: an investigation using network pharmacology and bioinformatics analysis.","authors":"Xiaocong Liang, Huiling Yang, Pengrong Hu, Ziyan Gan, Shunqin Long, Sumei Wang, Xiaobing Yang","doi":"10.1080/15376516.2024.2411621","DOIUrl":"10.1080/15376516.2024.2411621","url":null,"abstract":"<p><p>Moutan cortex has demonstrated antitumor properties attributed to its bioactive compound Paeoniflorigenone (PA). Nevertheless, there is limited research on the efficacy of PA in the prevention and treatment of hepatocellular carcinoma (HCC). We aimed to investigate the potential pharmacological mechanisms of PA in the treatment of Aflatoxin B1 (AFB1)-induced hepatocarcinogenesis using network pharmacology and bioinformatics analysis approaches. Through various databases and bioinformatics analysis approaches, 34 shared targets were identified as potential candidate genes for PA in fighting liver cancer caused by AFB1. Pathway analysis revealed involvement in cell cycle, HIF-1, and Rap1 pathways. A risk assessment model was developed using LASSO regression, showing an association between the identified genes and the tumor immune microenvironment. The genes within the risk model were found to be linked to the immune response in liver cancer. Molecular docking studies indicated that PA interacts with its targets through hydrogen bonding and hydrophobic interactions. This study provides insights into the possible mechanisms of PA in liver cancer treatment and offers a predictive model for assessing the risk level of individuals with liver cancer. These findings have significant implications for the therapeutic strategies in managing liver cancer patients.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-13"},"PeriodicalIF":3.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354441","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":"<i>Inonotus obliquus</i> aqueous extract inhibits intestinal inflammation and insulin metabolism defects in <i>Drosophila</i>.","authors":"Shichao Yu, Zhixian Lai, Hongmei Xue, Jiahua Zhu, Guanhua Yue, Jiewei Wang, Li Hua Jin","doi":"10.1080/15376516.2024.2368795","DOIUrl":"10.1080/15376516.2024.2368795","url":null,"abstract":"<p><p>In biomedical research, the fruit fly (<i>Drosophila melanogaster</i>) is among the most effective and flexible model organisms. Through the use of the <i>Drosophila</i> model, molecular mechanisms of human diseases can be investigated and candidate pharmaceuticals can be screened. White rot fungus <i>Inonotus obliquus</i> is a member of the family <i>Hymenochaetaceae</i>. Due to its multifaceted pharmacological effects, this fungus has been the subject of scientific investigation. Nevertheless, the precise mechanisms by which <i>Inonotus obliquus</i> treats diseases remain unclear. In this study, we prepared an aqueous extract derived from <i>Inonotus obliquus</i> and demonstrated that it effectively prevented the negative impacts of inflammatory agents on flies, including overproliferation and overdifferentiation of intestinal progenitor cells and decreased survival rate. Furthermore, elevated reactive oxygen species levels and cell death were alleviated by <i>Inonotus obliquus</i> aqueous extract, suggesting that this extract inhibited intestinal inflammation. Additionally, <i>Inonotus obliquus</i> aqueous extract had an impact on the insulin pathway, as it alleviated growth defects in flies that were fed a high-sugar diet and in <i>chico</i> mutants. In addition, we determined the composition of <i>Inonotus obliquus</i> aqueous extract and conducted a network pharmacology analysis in order to identify prospective key compounds and targets. In brief, <i>Inonotus obliquus</i> aqueous extract exhibited considerable potential as a therapeutic intervention for human diseases. Our research has established a foundational framework that supports the potential clinical implementation of <i>Inonotus obliquus</i>.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"970-984"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318366","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":"Spatial memory impairment is associated with decreased dopamine-β-hydroxylase activity in the brains of rats exposed to manganese chloride.","authors":"Valentina Mikhailovna Kudrinskaya, Andrey Pavlovich Ivlev, Daria Alexeevna Obukhova, Viktoriya Aleksandrovna Maystrenko, Tatiana Valentinovna Tiutiunnik, Dmitrii Sergeevich Traktirov, Marina Nikolaevna Karpenko, Irina Sergeevna Ivleva","doi":"10.1080/15376516.2024.2379012","DOIUrl":"10.1080/15376516.2024.2379012","url":null,"abstract":"<p><p>Chronic exposure to manganese compounds leads to accumulation of the manganese in the basal ganglia and hippocampus. High levels of manganese in these structures lead to oxidative stress, neuroinflammation, imbalance of brain neurotransmitters, and hyperactivation of calpains mediating neurotoxicity and causing motor and cognitive impairment. The purpose of this work was to study the effect of excess manganese chloride intake on rats' spatial memory and on dopamine-β-hydroxylase (DβH) activity under conditions of calpain activity suppression. Rats were divided into 3 groups of 10 animals each. Group 1 received MnCl₂ (30 days, 5 mg/kg/day, intranasally), group 2 received MnCl₂ (30 days, 5 mg/kg/day, intranasally) and calpain inhibitor Cast (184-210) (30 days, 5 µg/kg/day, intranasally), and group 3 received sterile saline (30 days in a volume of 20 μl, intranasally). The spatial working memory was assessed using Morris water maze test. DβH activity was determined by HPLC. We have shown that in response to excessive intake of MnCl₂, there was a development of cognitive impairments in rats, which was accompanied by a decrease in DβH activity in the hippocampus. The severity of cognitive impairment was reduced by inhibiting the activity of m-calpain. The protective effect of calpain inhibitors was achieved not through an effect on DβH activity. Thus, the development of therapeutic regimens for the treatment of manganism using dopaminomimetics and/or by inhibiting calpains, must be performed taking into account the manganese-induced decrease of DβH activity and the inability to influence this process with calpain inhibitors.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1035-1044"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634623","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":"Naturally-derived phenethyl isothiocyanate modulates apoptotic induction through regulation of the intrinsic cascade and resulting apoptosome formation in human malignant melanoma cells.","authors":"Venetia Tragkola, Ioannis Anestopoulos, Sotiris Kyriakou, Tom Amery, Rodrigo Franco, Aglaia Pappa, Mihalis I Panayiotidis","doi":"10.1080/15376516.2024.2369666","DOIUrl":"10.1080/15376516.2024.2369666","url":null,"abstract":"<p><p>Malignant melanoma is the most aggressive type of skin cancer with increasing incidence rates worldwide. On the other hand, watercress is a rich source of phenethyl isothiocyanate (PEITC), among others, which has been widely investigated for its anticancer properties against various cancers. In the present study, we evaluated the role of a watercress extract in modulating apoptotic induction in an <i>in vitro</i> model of human malignant melanoma consisting of melanoma (A375, COLO-679, COLO-800), non-melanoma epidermoid carcinoma (A431) and immortalized, non-tumorigenic keratinocyte (HaCaT) cells. Moreover, the chemical composition of the watercress extract was characterized through UPLC MS/MS and other analytical methodologies. In addition, cytotoxicity was assessed by the alamar blue assay whereas apoptosis was determined, initially, by a multiplex activity assay kit (measuring levels of activated caspases -3, -8 and -9) as well as by qRT-PCR for the identification of major genes regulating apoptosis. In addition, protein expression levels were evaluated by western immunoblotting. Our data indicate that the extract contains various phytochemicals (e.g. phenolics, flavonoids, pigments, etc.) while isothiocyanates (ITCs; especially PEITC) were the most abundant. In addition, the extract was shown to exert a significant time- and dose-dependent cytotoxicity against all malignant melanoma cell lines while non-melanoma and non-tumorigenic cells exhibited significant resistance. Finally, expression profiling revealed a number of genes (and corresponding proteins) being implicated in regulating apoptotic induction through activation of the intrinsic apoptotic cascade. Overall, our data indicate the potential of PEITC as a promising anti-cancer agent in the clinical management of human malignant melanoma.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"985-999"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451546","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":"Hesperetin protects against rotenone-induced motor disability and neurotoxicity via the regulation of SIRT1/NLRP3 signaling.","authors":"Hayam Ateyya, Huda M Atif, Noha M Abd El-Fadeal, Eman Abul-Ela, Rania I Nadeem, Nermin I Rizk, Fatma Alzahraa M Gomaa, Sozan M Abdelkhalig, Afaf A Aldahish, Manal S Fawzy, Bassant M Barakat, Sawsan A Zaitone","doi":"10.1080/15376516.2024.2390646","DOIUrl":"10.1080/15376516.2024.2390646","url":null,"abstract":"<p><p>Rotenone is a pesticide that causes complex I inhibition and is widely known to induce motor disability and experimental Parkinson's disease (PD) in rodents. Evidence suggests a crucial role for sirtuin/nuclear factor-kappaB/nod-like receptor family, pyrin domain-containing 3 (SIRT1/NFκB/NLRP3) signaling and inflammation in PD and rotenone neurotoxicity. Hesperetin (C16H14O6) is a citrus flavonoid with documented anti-inflammatory activity. We investigated the value of hesperetin in delaying rotenone-induced PD in mice and the possible modulation of inflammatory burden. PD was induced in mice <i>via</i> rotenone injections. Groups were assigned as a vehicle, PD, or PD + hesperetin (50 or 100 mg/kg) and compared for the motor function, protein level (by ELISA), and gene expression (by real-time PCR) of the target proteins, histopathology, and immunohistochemistry for tyrosine hydroxylase enzyme. Hesperetin (50 or 100 mg/kg) alleviated the motor disability and the striatal dopamine level and decreased the expression of <i>NLRP3</i> and <i>NF-κB</i> but increased <i>SIRT1</i> expression (<i>p</i> < 0.05). Further, it enhanced the neural viability and significantly decreased neural degeneration in the substantia nigra, hippocampus, and cerebral cortex (<i>p</i> < 0.05). Taken together, we propose that hesperetin mediates its neuroprotective function <i>via</i> alleviating modulation of the SIRT1/NFκB/NLRP3 pathway. Therefore, hesperetin might delay the PD progression.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1045-1060"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907721","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":"Metformin attenuates PM_2.5-induced oxidative stress by inhibiting the AhR/CYP1A1 pathway in proximal renal tubular epithelial cells.","authors":"Jing Cui, Weilin Chen, Dongdong Zhang, Mengqiu Lu, Zhijun Huang, Bin Yi","doi":"10.1080/15376516.2024.2378296","DOIUrl":"10.1080/15376516.2024.2378296","url":null,"abstract":"<p><p>The harmful effects of PM_2.5 on human health, including an increased risk of chronic kidney disease (CKD), have raised a lot of attention, but the underlying mechanisms are unclear. We used the Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS) to simulate the inhalation of PM_2.5 in the real environment and established an animal model by exposing C57BL/6 mice to filtered air (FA) and Particulate Matter (PM_2.5) for 8 weeks. PM_2.5 impaired the renal function of the mice, and the renal tubules underwent destructive changes. Analysis of NHANES data showed a correlation between reduced kidney function and higher blood levels of PM_2.5 components, polychlorinated biphenyls (PCBs) and dioxins, which are Aryl hydrocarbon Receptor (AhR) ligands. PM_2.5 exposure induced higher levels of AhR and CYP1A1 and oxidative stress as evidenced by the higher levels of ROS, MDA, and GSSG in kidneys of mice. PM_2.5 exposure led to AhR overexpression and nuclear translocation in proximal renal tubular epithelial cells. Inhibition of AhR reduced CYP1A1 expression and PM_2.5-increased levels of ROS, MDA and GSSG. Our study suggested metformin can mitigate PM_2.5-induced oxidative stress by inhibiting the AhR/CYP1A1 pathway. These findings illuminated the role of AhR/CYP1A1 pathway in PM_2.5-induced kidney injury and the protective effect of metformin on PM_2.5-induced cellular damage, offering new insights for air pollution-related renal diseases.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1022-1034"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735060","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":"Assessment of genotoxic damage induced by exposure to binary mixtures of polycyclic aromatic hydrocarbons and three heavy metals in male mice.","authors":"Norberto Alarcón-Herrera, Sandra Gómez-Arroyo, Saúl Flores-Maya, Ana Rosa Flores-Márquez, Paulina Abrica-González","doi":"10.1080/15376516.2024.2365434","DOIUrl":"10.1080/15376516.2024.2365434","url":null,"abstract":"<p><strong>Introduction: </strong>Heavy metals (HM) and polycyclic aromatic hydrocarbons (PAHs) exposition has been associated with health problems. Therefore, this research evaluated genotoxicity induced in male mice strain CD-1 exposed to benzo[a]anthracene (B[a]A) and benzo[a]pyrene (B[a]P) and their interaction with Fe, Pb, and Al.</p><p><strong>Methods: </strong>Groups of animals were exposed intraperitoneally to HM, PAHs, and mixtures of both. Peripheral blood samples were taken from 0 to 96 h at 24 h intervals; genotoxicity was determined by micronucleus tests and comet assay. Additionally, toxicity and viability were evaluated.</p><p><strong>Results: </strong>HM and PAHs individually were genotoxic. About toxicity, only Al altered polychromatic erythrocytes number and did not change leukocytes viability. Concerning mixtures, Fe + B[a]P, Fe + B[a]A, Pb + B[a]P increased genotoxicity. There were no changes with Pb + B[a]A. Finally, Al mixtures with both PAHs damage was decreased.</p><p><strong>Conclusions: </strong>Exposure to HM and PAH caused genetic damage. Fe, Al, and B[a]A, established a genotoxic potential. Every metal can interact with PAHs in different ways. Also, the micronucleus test and the comet assay demonstrated their high capacity and reliability to determine the genotoxic potential of the compounds evaluated in this work.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"955-969"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306933","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}