The carcinogenicity of several samples of mineral fibers was tested following injection of 20 mg in the pleural cavity of noninbred Sprague-Dawley rats. Three samples of chrysotile asbestos (mean length: 3.2, 2.1, and 1.2 micron) induced mesotheliomas at a rate of 48, 52, and 19%, respectively. The first sample was acid leached prior to intrapleural injection; in that group, the percentage of mesotheliomas was reduced to 25%. Treatment with amosite and crocidolite resulted in the occurrence of 57 and 56% of mesotheliomas. Acid-treatment of amphiboles did not significantly modify the percentage of mesotheliomas. When the Stanton's fiber dimensions were taken into consideration to correlate with mesothelioma incidence, the observed number of mesotheliomas in the chrysotile-treated animals was much lower than that expected, suggesting that other fiber parameters (chemistry, physicochemistry) play a role in the carcinogenicity. Attapulgite fibers (mean length: 0.77 micron) did not induce tumor, and the mean survival time was of the same order as that observed in the control groups. The injection of quartz resulted in no mesothelioma but did result in 6 malignant histiocytic lymphomas (17%) and 2 malignant schwannomas (6%). In vitro experiments did not show strong correlation between cytotoxicity and the carcinogenic potency of these minerals, but the qualitative cellular responses might give some indications on the fiber's potency. In addition, the in vitro effects of the fibers seem to be modulated by their size.
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Environ Toxicol Chem
January 2025
School of Environment Science and Spatial Informatics, China University of Mining and Technology, Xuzhou, China.
N-Nitrosamines are a class of compounds that includes the potent mutagenicity and carcinogenicity of many of its members and is distributed widely throughout the human environment. DNA alkylation by their diazonium ions formed metabolically acts as a molecular initiating event (MIE) that links molecular chemistry to mutagenicity. However, the regiochemistry for diazonium ions reacting with DNA bases is still under debate.
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January 2025
Graduate Toxicology Program, Department of Veterinary Sciences, Utah State University, Logan, UT 84322, USA.
It has been known since the early days of the discovery of aflatoxin B1 (AFB1) that there were large species differences in susceptibility to AFB1. It was also evident early on that AFB1 itself was not toxic but required bioactivation to a reactive form. Over the past 60 years there have been thousands of studies to delineate the role of ~10 specific biotransformation pathways of AFB1, both phase I (oxidation, reduction) and phase II (hydrolysis, conjugation, secondary oxidations, and reductions of phase I metabolites).
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March 2025
Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Clinical Research Development Unit of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, Iran; Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran. Electronic address:
Hepatocellular carcinoma (HCC) is the primary malignancy affecting the liver and the leading cause of mortality among individuals with cirrhosis. This complex disease is associated with various risk factors, including environmental, pathological, and genetic influences, which dysregulate gene expression crucial for the cell cycle and cellular/molecular pathways. The disruption of the balance between tumor suppressors and proto-oncogenes amplifies the pathogenic cascade.
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February 2025
Jiangsu Key Laboratory of Drug Design & Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, PR China. Electronic address:
Dysregulation of the fibroblast growth factor receptor 1 (FGFR1) signaling has prompted efforts to develop therapeutic agents, which is a carcinogenic driver of many cancers, including breast, prostate, bladder, and chronic myeloid leukemia. Despite significant progress in the development of potent and selective FGFR inhibitors, the long-term efficacy of these drugs in cancer therapy has been hampered by the rapid onset of acquired resistance. Therefore, more drug discovery strategies are needed to promote the development of FGFR-targeted drugs.
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January 2025
National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, 72079, USA.
Several potent carcinogenic nitrosamines, including N-nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA), induce micronuclei in the micronucleated hepatocyte (MNHEP) assay but not in the micronucleated reticulocyte (MNRET) assay. However, the MNHEP assay is not as frequently used as the MNRET assay for evaluating in vivo genotoxicity. The present study evaluated MN formation in the liver of Big Blue transgenic rats exposed to four small-molecule nitrosamines, NDMA, N-nitrosodiisopropylamine (NDIPA), N-nitrosoethylisoporpylamine (NEIPA), and N-nitrosomethylphenylamine (NMPA), using a repeat-dose protocol typically used for in vivo mutagenicity studies.
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