Hexavalent chromium (chromate) is a potent human carcinogen that is present in the workplace of about 500,000 U.S. workers and at several hundred Superfund sites. Drinking water contamination and particulate ambient pollution are two other significant sources of human exposure to Cr-6. Assessment of individual doses of Cr-6 would greatly improve understanding of risks associated with environmental contamination and alleviate public concerns about the extent of the actual human exposures. Because Cr-6 is reduced in human body to Cr-3, measurements of total Cr levels in biological specimens are unable to differentiate between exposures to carcinogenic Cr-6 and ubiquitous forms of nontoxic Cr-3. Thus, the main approach to the estimation of human exposure to toxic Cr compounds should be based on the analysis of specific biological changes caused by Cr-6. Cr-DNA adducts are a unique form of DMA modifications produced by Cr-6 in human cells and therefore, they offer a potential to serve as highly specific indicators of individual doses of Cr-6. Our recent findings demonstrated that cellular reduction of Cr-6 by vitamin C was a principal route to high mutagenicity and genotoxicity of this metal. These results led to the uncertainty in the development of Cr-6 biomarkers as we poorly understand which Cr-DNA adduct(s) are most important toxicologically in cells containing vitamin C. The main goal of this project is to identify the most potent mutagenic and genotoxic Cr-DNA adducts arising from reductive metabolism of Cr-6 by cellular ascorbate.
Three Specific Aims will examine (i) the formation of mutagenic Cr-DNA adducts in human lung cells, (ii) the relationship between mutagenicity and genotoxicity of bulky Cr-DNA adducts, and (iii) mechanisms of hypersensitivity of ascorbatesupplemented cells to Cr-6 compounds. The results of proposed studies are expected to provide the basis for the development of mechanistically important, specific biodosimeters of human exposure to different chemical and physical forms of hexavalent chromium.
The over-arching goal of this Superfund Basic Research Program is to address health concerns, and to design novel remediation techniques, related to mixed exposures arising from contaminated lands and buildings, using Rhode Island as a model for appropriate research, educational, and training interventions.
|Toral-Sánchez, E; Rangel-Mendez, J R; Hurt, Robert H et al. (2018) Novel application of magnetic nano-carbon composite as redox mediator in the reductive biodegradation of iopromide in anaerobic continuous systems. Appl Microbiol Biotechnol 102:8951-8961|
|Thompson, Marcella Remer; Schwartz Barcott, Donna (2018) The Role of the Nurse Scientist as a Knowledge Broker. J Nurs Scholarsh :|
|Spade, Daniel J; Dere, Edward; Hall, Susan J et al. (2018) All-trans retinoic acid disrupts development in ex vivo cultured fetal rat testes. I: Altered seminiferous cord maturation and testicular cell fate. Toxicol Sci :|
|Spade, Daniel J; Bai, Cathy Yue; Lambright, Christy et al. (2018) Validation of an automated counting procedure for phthalate-induced testicular multinucleated germ cells. Toxicol Lett 290:55-61|
|Sears, Clara G; Braun, Joseph M; Ryan, Patrick H et al. (2018) The association of traffic-related air and noise pollution with maternal blood pressure and hypertensive disorders of pregnancy in the HOME study cohort. Environ Int 121:574-581|
|Guelfo, Jennifer L; Adamson, David T (2018) Evaluation of a national data set for insights into sources, composition, and concentrations of per- and polyfluoroalkyl substances (PFASs) in U.S. drinking water. Environ Pollut 236:505-513|
|Guelfo, Jennifer L; Marlow, Thomas; Klein, David M et al. (2018) Evaluation and Management Strategies for Per- and Polyfluoroalkyl Substances (PFASs) in Drinking Water Aquifers: Perspectives from Impacted U.S. Northeast Communities. Environ Health Perspect 126:065001|
|Chen, Po-Yen; Zhang, Mengke; Liu, Muchun et al. (2018) Ultrastretchable Graphene-Based Molecular Barriers for Chemical Protection, Detection, and Actuation. ACS Nano 12:234-244|
|Wilson, Shelby; Dere, Edward; Klein, David et al. (2018) Localization of dimethylated histone three lysine four in the Rattus norvegicus sperm genome. Biol Reprod 99:266-268|
|Kane, Agnes B; Hurt, Robert H; Gao, Huajian (2018) The asbestos-carbon nanotube analogy: An update. Toxicol Appl Pharmacol 361:68-80|
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