AKR1C2 genetic variants mediate tobacco carcinogens metabolism involving bladder cancer susceptibility
In this study, we derived TCMGs from metabolic pathways of polycyclic aromatic hydrocarbons and tobacco-specific nitrosamines, and then explored genetic associations between TCMGs and bladder cancer risk in two populations: a Chinese population of 580 cases and 1101 controls, and a European population of 5930 cases and 5468 controls, along with interaction and joint analyses. Expression patterns of TCMGs were sourced from Nanjing Bladder Cancer (NJBC) study and publicly available datasets. Among 43 TCMGs, we observed that rs7087341 T > A in AKR1C2 was associated with a reduced risk of bladder cancer in the Chinese popul...
Source: Archives of Toxicology - April 25, 2024 Category: Toxicology Authors: Yanping Xiao Yang Shen Hui Song Fang Gao Zhenguang Mao Qiang Lv Chao Qin Lin Yuan Dongmei Wu Haiyan Chu Meilin Wang Mulong Du Rui Zheng Zhengdong Zhang Source Type: research
The characteristics, occurrence, and toxicological effects of alternariol: a mycotoxin
Arch Toxicol. 2024 Apr 25. doi: 10.1007/s00204-024-03743-0. Online ahead of print.ABSTRACTAlternaria species are mycotoxin-producing fungi known to infect fresh produce and to cause their spoilage. Humans get exposed to fungal secondary metabolites known as mycotoxin via the ingestion of contaminated food. Alternariol (AOH) (C14H10O5) is an isocoumarins produced by different species of Alternaria including Alternaria alternata. AOH is often found in grain, fruits and fruits-based food products with high levels in legumes, nuts, and tomatoes. AOH was first discovered in 1953, and it is nowadays linked to esophagus cancer an...
Source: Archives of Toxicology - April 25, 2024 Category: Toxicology Authors: Iman Saleh Randa Zeidan Mohammed Abu-Dieyeh Source Type: research
In vitro to in vivo extrapolation to derive a metabolism factor for estimating the aggregate exposure to salicylic acid after dermal exposure of its esters
In conclusion, these results indicate that not all substances contribute equally (or at all) to the systemic exposure to salicylic acid. Therefore, we propose a realistic metabolism correction factor by which the potential contribution of salicylate esters to the aggregate consumer exposure to salicylic acid from cosmetic use can be estimated.PMID:38658404 | DOI:10.1007/s00204-024-03749-8 (Source: Archives of Toxicology)
Source: Archives of Toxicology - April 24, 2024 Category: Toxicology Authors: Abdulkarim Najjar Sebastien Gr égoire Beate Nicol Andreas Natsch Nazanin Golbamaki Fanny Boisleve Amaia Irizar Brian Wall Angus Swinscoe Val érie Masini-Etévé Dan Selechnik Anne Marie Api Peter Griem Nicola Hewitt Estefania Cardamone Source Type: research
Vascular endothelial dysfunction induced by 3-bromofluoranthene via MAPK-mediated-NF κB pro-inflammatory pathway and intracellular ROS generation
In conclusion, 3-BrFlu is a hazardous substance that results in vascular endothelial dysfunction through the MAPK-mediated-NFκB pro-inflammatory pathway and intracellular ROS generation.PMID:38635053 | DOI:10.1007/s00204-024-03751-0 (Source: Archives of Toxicology)
Source: Archives of Toxicology - April 18, 2024 Category: Toxicology Authors: Chien-Ying Lee Sheng-Wen Wu Jiann-Jou Yang Wen-Ying Chen Chun-Jung Chen Hsin-Hung Chen Yi-Chia Lee Chun-Hung Su Yu-Hsiang Kuan Source Type: research
Vascular endothelial dysfunction induced by 3-bromofluoranthene via MAPK-mediated-NF κB pro-inflammatory pathway and intracellular ROS generation
In conclusion, 3-BrFlu is a hazardous substance that results in vascular endothelial dysfunction through the MAPK-mediated-NFκB pro-inflammatory pathway and intracellular ROS generation.PMID:38635053 | DOI:10.1007/s00204-024-03751-0 (Source: Archives of Toxicology)
Source: Archives of Toxicology - April 18, 2024 Category: Toxicology Authors: Chien-Ying Lee Sheng-Wen Wu Jiann-Jou Yang Wen-Ying Chen Chun-Jung Chen Hsin-Hung Chen Yi-Chia Lee Chun-Hung Su Yu-Hsiang Kuan Source Type: research
Vascular endothelial dysfunction induced by 3-bromofluoranthene via MAPK-mediated-NF κB pro-inflammatory pathway and intracellular ROS generation
In conclusion, 3-BrFlu is a hazardous substance that results in vascular endothelial dysfunction through the MAPK-mediated-NFκB pro-inflammatory pathway and intracellular ROS generation.PMID:38635053 | DOI:10.1007/s00204-024-03751-0 (Source: Archives of Toxicology)
Source: Archives of Toxicology - April 18, 2024 Category: Toxicology Authors: Chien-Ying Lee Sheng-Wen Wu Jiann-Jou Yang Wen-Ying Chen Chun-Jung Chen Hsin-Hung Chen Yi-Chia Lee Chun-Hung Su Yu-Hsiang Kuan Source Type: research
Toxicity of cannabidiol and its metabolites in TM3 mouse Leydig cells: a comparison with primary human Leydig cells
In this study, we investigated the effects of CBD and its metabolites on TM3 mouse Leydig cells. CBD, at concentrations below 30 µM, reduced cell viability, induced G1 cell cycle arrest, and inhibited DNA synthesis. CBD induced apoptosis after exposure to high concentrations (≥ 50 µM) for 24 h or a low concentration (20 µM) for 6 days. 7-Hydroxy-CBD and 7-carboxy-CBD, the main CBD metabolites of CBD, exhibited the similar toxic effects as CBD. In addition, we conducted a time-course mRNA-sequencing analysis in both primary human Leydig cells and TM3 mouse Leydig cells to understand and compare the mechanisms underlyin...
Source: Archives of Toxicology - April 17, 2024 Category: Toxicology Authors: Yuxi Li Qiangen Wu Xilin Li Patrick Cournoyer Supratim Choudhuri Lei Guo Si Chen Source Type: research
Characterizing the toxicological responses to inorganic arsenicals and their metabolites in immortalized human bladder epithelial cells
Arch Toxicol. 2024 Apr 17. doi: 10.1007/s00204-024-03750-1. Online ahead of print.ABSTRACTArsenic is highly toxic to the human bladder. In the present study, we established a human bladder epithelial cell line that closely mimics normal human bladder epithelial cells by immortalizing primary uroplakin 1B-positive human bladder epithelial cells with human telomerase reverse transcriptase (HBladEC-T). The uroplakin 1B-positive human bladder epithelial cell line was then used to evaluate the toxicity of seven arsenicals (iAsV, iAsIII, MMAV, MMAIII, DMAV, DMAIII, and DMMTAV). The cellular uptake and metabolism of each arsenica...
Source: Archives of Toxicology - April 17, 2024 Category: Toxicology Authors: Arpamas Vachiraarunwong Min Gi Tohru Kiyono Shugo Suzuki Masaki Fujioka Guiyu Qiu Runjie Guo Tomoki Yamamoto Anna Kakehashi Masayuki Shiota Hideki Wanibuchi Source Type: research
The rat acute oral toxicity of trifluoromethyl compounds (TFMs): a computational toxicology study combining the 2D-QSTR, read-across and consensus modeling methods
Arch Toxicol. 2024 Apr 16. doi: 10.1007/s00204-024-03739-w. Online ahead of print.ABSTRACTAll areas of the modern society are affected by fluorine chemistry. In particular, fluorine plays an important role in medical, pharmaceutical and agrochemical sciences. Amongst various fluoro-organic compounds, trifluoromethyl (CF3) group is valuable in applications such as pharmaceuticals, agrochemicals and industrial chemicals. In the present study, following the strict OECD modelling principles, a quantitative structure-toxicity relationship (QSTR) modelling for the rat acute oral toxicity of trifluoromethyl compounds (TFMs) was e...
Source: Archives of Toxicology - April 16, 2024 Category: Toxicology Authors: Xinyi Lu Xin Wang Shuo Chen Tengjiao Fan Lijiao Zhao Rugang Zhong Guohui Sun Source Type: research
The rat acute oral toxicity of trifluoromethyl compounds (TFMs): a computational toxicology study combining the 2D-QSTR, read-across and consensus modeling methods
Arch Toxicol. 2024 Apr 16. doi: 10.1007/s00204-024-03739-w. Online ahead of print.ABSTRACTAll areas of the modern society are affected by fluorine chemistry. In particular, fluorine plays an important role in medical, pharmaceutical and agrochemical sciences. Amongst various fluoro-organic compounds, trifluoromethyl (CF3) group is valuable in applications such as pharmaceuticals, agrochemicals and industrial chemicals. In the present study, following the strict OECD modelling principles, a quantitative structure-toxicity relationship (QSTR) modelling for the rat acute oral toxicity of trifluoromethyl compounds (TFMs) was e...
Source: Archives of Toxicology - April 16, 2024 Category: Toxicology Authors: Xinyi Lu Xin Wang Shuo Chen Tengjiao Fan Lijiao Zhao Rugang Zhong Guohui Sun Source Type: research
Tl(I) and Tl(III)-induce genotoxicity, reticulum stress and autophagy in PC12 Adh cells
Arch Toxicol. 2024 Apr 15. doi: 10.1007/s00204-024-03752-z. Online ahead of print.ABSTRACTThallium (Tl) and its two cationic species, Tl(I) and Tl(III), are toxic for most living beings. In this work, we investigated the effects of Tl (10-100 µM) on the viability and proliferation capacity of the adherent variant of PC12 cells (PC12 Adh cells). While both Tl(I) and Tl(III) halted cell proliferation from 24 h of incubation, their viability was ~ 90% even after 72 h of treatment. At 24 h, increased levels of γH2AX indicated the presence of DNA double-strand breaks. Simultaneously, increased expression of p53 and its phosph...
Source: Archives of Toxicology - April 15, 2024 Category: Toxicology Authors: Damiana M Salvatierra-Fr échou Sandra V Verstraeten Source Type: research
Harnessing machine learning to predict cytochrome P450 inhibition through molecular properties
In this study, three different molecular or substructural properties that include Morgan, MACCS and Morgan (combined) and RDKit of the various molecules are used to train a distinct SVM model against each isozyme (1A2, 2C9, 2C19, 2D6, and 3A4). On the independent dataset, Morgan fingerprints provided the best results, while MACCS and Morgan (combined) achieved comparable results in terms of balanced accuracy (BA), sensitivity (Sn), and Mathews correlation coefficient (MCC). For the Morgan fingerprints, balanced accuracies (BA), Mathews correlation coefficients (MCC), and sensitivities (Sn) against each CYPs isozyme, 1A2, 2...
Source: Archives of Toxicology - April 15, 2024 Category: Toxicology Authors: Hamza Zahid Hilal Tayara Kil To Chong Source Type: research
Repeated-dose toxicity and toxicokinetic study of isobutylparaben in rats subcutaneously treated for 13 weeks
This study aimed to evaluate the prolonged systemic toxicity, semen quality, and estrus cycle in relation to endocrine disruption endpoints, alongside assessing the toxicokinetic behavior of IBP in Sprague-Dawley rats following a 13-week repeated subcutaneous administration. The rats were administered either the vehicle (4% Tween 80) or IBP at dosage levels of 2, 10, and 50 mg/kg/day for 13 weeks. Blood collection for toxicokinetic study was conducted on three specified days: day 1 (1st), day 30 (2nd), and day 91 (3rd). Systemic toxicity assessment and potential endocrine effects were based on various parameters including ...
Source: Archives of Toxicology - April 15, 2024 Category: Toxicology Authors: Jung Dae Lee Jin-Sook Bae Hyang Yeon Kim Si-Whan Song Jong-Choon Kim Byung-Mu Lee Kyu-Bong Kim Source Type: research
Higher paracetamol levels are associated with elevated glucocorticoid concentrations in hair: findings from a large cohort of young adults
This study addresses this gap by investigating associations between steroid hormones (cortisol, cortisone, and testosterone) and paracetamol concentrations measured in human hair, indexing a timeframe of approximately three months. The data came from a large community sample of young adults (N = 1002). Hair data were assayed using liquid chromatography-tandem mass spectrometry. Multiple regression models tested associations between paracetamol and steroid hormones, while adjusting for a wide range of potential confounders, such as sex, stressful live events, psychoactive substance use, hair colour, and body mass index. Alm...
Source: Archives of Toxicology - April 14, 2024 Category: Toxicology Authors: Lydia Johnson-Ferguson Lilly Shanahan Michelle Loher Laura Bechtiger Tina M Binz Markus Baumgartner Denis Ribeaud Manuel Eisner Boris B Quednow Source Type: research
Sub-acute oral exposure to lowest observed adverse effect level of nivalenol exacerbates atopic dermatitis in mice via direct activation of mitogen-activated protein kinase signal in antigen-presenting cells
This study investigated the immunotoxic effects of the mycotoxin nivalenol (NIV) using antigen-presenting cells and a mouse model of atopic dermatitis (AD). In vitro experiments were conducted using a mouse macrophage cell line (RAW 264.7) and mouse dendritic cell line (DC 2.4). After cells were exposed to NIV (0.19-5 µmol) for 24 h, the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNFα) was quantified. To further investigate the inflammatory cytokine production pathway, the possible involvement of mitogen-activated protein kinase (MAPK) pathways, such as ERK1/2, p-38, and JNK, in NIV exposure was analyzed...
Source: Archives of Toxicology - April 14, 2024 Category: Toxicology Authors: Reo Matsuzaka Hiroki Yamaguchi Chiharu Ohira Tomoe Kurita Naoki Iwashita Yoshiichi Takagi Tomomi Nishino Kyoko Noda Kazutoshi Sugita Masayo Kushiro Shiro Miyake Tomoki Fukuyama Source Type: research
