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Keywords = urinary 8-OHdG adduct

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16 pages, 3402 KiB  
Article
Evaluation of the Mechanisms Involved in the Development of Bladder Toxicity following Exposure to Occupational Bladder Cancer Causative Chemicals Using DNA Adductome Analysis
by Shugo Suzuki, Min Gi, Masami Komiya, Asuka Obikane, Arpamas Vachiraarunwong, Masaki Fujioka, Anna Kakehashi, Yukari Totsuka and Hideki Wanibuchi
Biomolecules 2024, 14(1), 36; https://doi.org/10.3390/biom14010036 - 26 Dec 2023
Cited by 9 | Viewed by 2106
Abstract
Occupational exposure to aromatic amines (AAs) is an important risk factor for urinary bladder cancer. This study aimed to evaluate the toxicity of AAs and analyze the carcinogenic mechanisms in rat bladder by comprehensive analysis of DNA adducts (DNA adductome). DNA was extracted [...] Read more.
Occupational exposure to aromatic amines (AAs) is an important risk factor for urinary bladder cancer. This study aimed to evaluate the toxicity of AAs and analyze the carcinogenic mechanisms in rat bladder by comprehensive analysis of DNA adducts (DNA adductome). DNA was extracted from the bladder epithelia of rats treated with AAs, including acetoacet-o-toluidine (AAOT) and o-toluidine (OTD), and adductome analysis was performed. Principal component analysis–discriminant analysis revealed that OTD and AAOT observed in urinary bladder hyperplasia could be clearly separated from the controls and other AAs. After confirming the intensity of each adduct, four adducts were screened as having characteristics of the OTD/AAOT treatment. Comparing with the in-house DNA adduct database, three of four candidates were identified as oxidative DNA adducts, including 8-OH-dG, based on mass fragmentation together with high-resolution accurate mass (HRAM) spectrometry data. Therefore, findings suggested that oxidative stress may be involved in the toxicity of rat bladder epithelium exposed to AAs. Consequently, the administration of apocynin, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase, in six-week-old rats fed with 0.6% OTD in their diet resulted in simple hyperplastic lesions in the bladder that were suppressed by apocynin. The labeling indices of Ki67, γ-H2AX, and 8-OHdG were significantly decreased in an apocynin concentration-dependent manner. These findings indicate that oxidative stress may have contributed to the development of urinary cancer induced by OTD. Full article
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13 pages, 1300 KiB  
Article
Genotoxic Biomonitoring in Children Living near the El Fraile Mine Tailings in Northern Guerrero State, Mexico
by María Elena Calderon-Segura, Alejandro Ramírez-Guzmán, Oscar Talavera-Mendoza, Yolanda Carbajal-López, María del Carmen Martínez-Valenzuela, Martha Elena Mora-Herrera, Liliana Salinas-Alcántara and Patricia Hurtado-Brito
Toxics 2022, 10(11), 674; https://doi.org/10.3390/toxics10110674 - 8 Nov 2022
Cited by 5 | Viewed by 1776
Abstract
A genotoxic study was conducted with 101 elementary school children (56 girls and 45 boys) in the 6–7, 8–9, and 10–12 age ranges from El Fraile rural community, which is located beside the El Fraile mine tailings in Taxco of Alarcon City, in [...] Read more.
A genotoxic study was conducted with 101 elementary school children (56 girls and 45 boys) in the 6–7, 8–9, and 10–12 age ranges from El Fraile rural community, which is located beside the El Fraile mine tailings in Taxco of Alarcon City, in northern Guerrero State, Mexico. For this, we used the alkaline comet assay in exfoliated buccal mucosa cells, scoring three genotoxic parameters: tail intensity, tail moment, and tail length. Additionally, we detected oxidative DNA damage through urinary 8-OHdG levels by enzyme-linked immunosorbent assay. We also evaluated a control group consisting of 101 children in the same age ranges from Chilpancingo City, Guerrero, who had never lived near mining zones. Genotoxic results showed that there was a significant increase in three genotoxic parameters and urinary 8-OHdG levels in the exposed children group compared with the control group. Analysis of MANOVA revealed that boys aged 8 and 9 years had higher DNA damage than girls from the same exposure group, and Spearman’s analysis identified a positive correlation between DNA damage and sex and age. This study provides the first valuable genotoxic data in children living in areas with environmental pollution. Full article
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