Papers by Jennifer Toyoda
Toxicology and applied pharmacology, Jun 1, 2024
Toxicological sciences, Jun 12, 2024
Water, May 20, 2024
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Toxicological sciences, Mar 27, 2024
Toxicology and applied pharmacology, Mar 1, 2024
International Journal of Molecular Sciences, Dec 22, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Toxicological sciences : an official journal of the Society of Toxicology, Sep 22, 2016
Genomic instability is one of the primary models of carcinogenesis and a feature of almost all ca... more Genomic instability is one of the primary models of carcinogenesis and a feature of almost all cancers. Homologous recombination (HR) repair protects against genomic instability by maintaining high genomic fidelity during the repair of DNA double strand breaks. The defining step of HR repair is the formation of the Rad51 nucleofilament, which facilitates the search for a homologous sequence and invasion of the template DNA strand. Particulate hexavalent chromium (Cr(VI)), a human lung carcinogen, induces DNA double strand breaks and chromosome instability. Since the loss of HR repair increases Cr(VI)-induced chromosome instability, we investigated the effect of extended Cr(VI) exposure on HR repair. We show acute (24 h) Cr(VI) exposure induces a normal HR repair response. In contrast, prolonged (120 h) exposure to particulate Cr(VI) inhibited HR repair and Rad51 nucleofilament formation. Prolonged Cr(VI) exposure had a profound effect on Rad51, evidenced by reduced protein levels an...
myself fortunate to have found the Wise Laboratory of Environmental and Genetic Toxicology. I mus... more myself fortunate to have found the Wise Laboratory of Environmental and Genetic Toxicology. I must thank my mentor, John Pierce Wise, Sr., for guiding me during this journey. His advice and leadership shaped me as a researcher, buttressed my confidence, and equipped me with a toolbox of technical and soft skills that make me a stronger scientist. Whether I was hand-grabbing alligators from the side of a moving airboat, struggling with an uncooperative molecular assay, or navigating interpersonal challenges, John was there to encourage me. I am beyond grateful for all the lab members who were more than co-workers and became close friends. Thank you to Sandra Wise, Rachel Speer, and Taylor Croom-Pérez who provided patient and thorough training to me as a new scientist and set the example for me as a lab member. The graduate students, postdoctoral fellows, and medical school trainees I shared the lab with have contributed to the generation of my data through conducting third repeats and offering assistance and advice. Thank you to Haiyan Lu, Idoia Meaza, Aggie Williams, Hannah v Jaggers, Caitlin Cahill, John Wise, Jr., and Jamie Young. Thank you to Alicia Bolt with assistance in flow cytometry experiments.
Toxicology and Applied Pharmacology
Toxicology and Applied Pharmacology, 2022
Hexavalent chromium [Cr(VI)] is a global environmental pollutant and human lung carcinogen. Howev... more Hexavalent chromium [Cr(VI)] is a global environmental pollutant and human lung carcinogen. However, the mechanisms of Cr(VI) carcinogenesis are not well defined. Cr(VI)-altered gene expression has been reported in the literature and is implicated in numerous mechanisms of Cr(VI) carcinogenesis. MicroRNAs (miRNAs) play a key role in controlling gene expression and are associated with carcinogenic mechanisms. To date no studies have evaluated global changes in miRNA expression in human cells after Cr(VI) exposure. We used RNA sequencing to evaluate how a particulate Cr(VI) compound (zinc chromate), the most potent form of Cr(VI), alters global miRNA expression after acute (24 h) or prolonged (72 and 120 h) exposure to 0.1, 0.2 and 0.3 μg/cm2 zinc chromate in an immortalized, non-cancerous human lung cell line (WTHBF-6). Particulate Cr(VI) significantly affected expression of miRNAs at all time points and concentrations tested. We also found the number of significantly downregulated miRNAs increased in a time- and concentration-dependent manner and many miRNAs were upregulated after 24 h exposure at the intermediate concentration tested. Pathway analyses of the differentially expressed miRNAs predicted miRNAs target pathways of Cr(VI) carcinogenesis in a time- and concentration-dependent manner. These data are the first to evaluate global changes in miRNA expression in human lung cells after Cr(VI) exposure and indicate miRNAs may play a key role in pathways of Cr(VI) carcinogenesis.
BACKGROUND Hexavalent chromium [Cr(VI)] is a human lung carcinogen and global marine pollutant. H... more BACKGROUND Hexavalent chromium [Cr(VI)] is a human lung carcinogen and global marine pollutant. High Cr concentrations, resembling the ones observed in occupationally exposed workers, have been observed in fin whales (Balaenoptera physalus) in the Gulf of Maine. This outcome suggests Cr might be disrupting the health of fin whale populations. Indeed, Cr in acute (24 h) exposure does cause toxicity in fin whale cells. However, human cell culture data indicate prolonged exposures (120 h) induce a higher amount of toxicity compared to 24 h exposure due to an inhibition of homologous recombination repair. However, whether prolonged exposure causes similar outcomes in fin whale cells is unknown. OBJECTIVE Due to the importance of assessing prolonged exposure toxicity, this study focuses on characterizing acute and prolonged exposure of Cr(VI) in male and female fin whale cells. METHODS Cytotoxicity was measured by the clonogenic assay, also known as colony forming assay, which measures t...
Lung cancer is the leading cause of cancer death; however, the mechanisms of lung carcinogens are... more Lung cancer is the leading cause of cancer death; however, the mechanisms of lung carcinogens are poorly understood. Metals, including hexavalent chromium [Cr(VI)], induce chromosome instability, an early event in lung cancer. Failure of homologous recombination repair is a key mechanism for chromosome instability. Particulate Cr(VI) causes DNA double strand breaks and prolonged exposure impairs homologous recombination targeting a key effector protein in this pathway, RAD51. Reduced RAD51 protein is a key endpoint of particulate Cr(VI) exposure. It is currently unknown how Cr(VI) reduces RAD51 protein. E2F1 is the predominant transcription factor for RAD51. This study sought to identify if E2F1 modulates the RAD51 response to particulate Cr(VI). Particulate Cr(VI) reduced RAD51 protein and mRNA levels but had a minimal effect on RAD51 half-life. E2F1 protein and mRNA were also inhibited by particulate Cr(VI) exposure. To connect these two outcomes we tested if modulating E2F1 affec...
Frontiers in Environmental Science
Microplastics are ubiquitous pollutants in the marine environment and a health concern. They are ... more Microplastics are ubiquitous pollutants in the marine environment and a health concern. They are generated directly for commercial purposes or indirectly from the breakdown of larger plastics. Examining a toxicological profile for microplastics is a challenge due to their large variety of physico-chemical properties and toxicological behavior. In addition to their concentration, other parameters such as polymer type, size, shape and color are important to consider in their potential toxicity. Microplastics can adsorb pollutants such as polycyclic aromatic hydrocarbons (PAHs) or metals on their surface and are likely to contain plastic additives that add to their toxicity. The observations of microplastics in seafood increased concern for potential human exposure. Since literature considering microplastics in humans is scarce, using a One Environmental Health approach can help better inform about potential human exposures. Marine mammals and sea turtles are long-lived sentinel specie...
Hexavalent chromium [Cr(VI)] is a widespread environmental and occupational carcinogen. The mecha... more Hexavalent chromium [Cr(VI)] is a widespread environmental and occupational carcinogen. The mechanism of carcinogenesis remains poorly understood, but chromosome instability (CIN) is the dominant theory. How numerical CIN arises is unclear, but it correlates with centrosome amplification. Both phenotypes are hallmarks of cancers, early events in carcinogenesis, and have been shown to occur after Cr(VI) exposure to human skin and lung fibroblasts. In this study, we investigate numerical CIN and centrosome amplification in whale cells. Whales are our closest marine relatives, have long lifespans, and are exposed to environmental Cr(VI). Importantly, they have low cancer rates and cell culture studies show they are resistant to Cr(VI) genotoxicity. iv This study found increasing concentrations and prolonged exposure to zinc chromate produced no increase in aneuploid metaphases or centrosome amplification in interphase or mitotic cells. A concentration-dependent increase in cytotoxicity was measured, but no change in relative survival occurred with prolonged exposure. v
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Papers by Jennifer Toyoda