Exposure to genotoxic agents can occur from av variety of occupational and environmental sources. Enzymatic activation of these agents results in the formation of electrophiles which can subsequently react to form DNA adducts. The formation of DNA adducts is believed to play an important role in the activation of human oncogenes and the initiation of cancer. In these studies we will study the activation of benzene to form DNA damage.
The specific aims of this proposal are to investigate; 1. the formation and repair of DNA adducts, and 8-oxodeoxyguanosine in bone marrow and peripheral blood leukocytes of B6C3F1 mice treated with benzene by itself or in combination with other agents. 2. the formation of DNA damage in myeloid fractions of bone marrow of B6C3F1 mice and in collaboration with Projects 4 and 5 blood progenitor cells and peripheral blood cultures will be treated in vitro with benzene metabolites. 3. with Project 9, the dose response relationships between DNA adduct formation and reproductive, and developmental responses in aquatic organisms., 4. the formation of lacI mutations in the bone marrow ob Big Blue B6C3F1 mice treated with benzene. 5. with project 3, to optimize the procedures for structural identification of DNA adducts detected by 32P-postlabeling and identification of the structures of the DNA adducts formed by the benzene metabolites. These studies will provide a better understanding of the application of DNA adduct measurements as a molecular dosimeter for exposure to genotoxic agents.
Smith, Allan H; Marshall, Guillermo; Roh, Taehyun et al. (2018) Lung, Bladder, and Kidney Cancer Mortality 40?Years After Arsenic Exposure Reduction. J Natl Cancer Inst 110:241-249 |
Castriota, Felicia; Acevedo, Johanna; Ferreccio, Catterina et al. (2018) Obesity and increased susceptibility to arsenic-related type 2 diabetes in Northern Chile. Environ Res 167:248-254 |
Rothman, Nathaniel; Zhang, Luoping; Smith, Martyn T et al. (2018) Formaldehyde, Hematotoxicity, and Chromosomal Changes-Response. Cancer Epidemiol Biomarkers Prev 27:120-121 |
Yik-Sham Chung, Clive; Timblin, Greg A; Saijo, Kaoru et al. (2018) Versatile Histochemical Approach to Detection of Hydrogen Peroxide in Cells and Tissues Based on Puromycin Staining. J Am Chem Soc 140:6109-6121 |
Rappaport, Stephen M (2018) Redefining environmental exposure for disease etiology. NPJ Syst Biol Appl 4:30 |
Tachachartvanich, Phum; Sangsuwan, Rapeepat; Ruiz, Heather S et al. (2018) Assessment of the Endocrine-Disrupting Effects of Trichloroethylene and Its Metabolites Using in Vitro and in Silico Approaches. Environ Sci Technol 52:1542-1550 |
Guyton, Kathryn Z; Rieswijk, Linda; Wang, Amy et al. (2018) Key Characteristics Approach to Carcinogenic Hazard Identification. Chem Res Toxicol : |
Roh, Taehyun; Steinmaus, Craig; Marshall, Guillermo et al. (2018) Age at Exposure to Arsenic in Water and Mortality 30-40 Years After Exposure Cessation. Am J Epidemiol 187:2297-2305 |
Daniels, Sarah I; Chambers, John C; Sanchez, Sylvia S et al. (2018) Elevated Levels of Organochlorine Pesticides in South Asian Immigrants Are Associated With an Increased Risk of Diabetes. J Endocr Soc 2:832-841 |
Guyton, Kathryn Z; Rusyn, Ivan; Chiu, Weihsueh A et al. (2018) Application of the key characteristics of carcinogens in cancer hazard identification. Carcinogenesis 39:614-622 |
Showing the most recent 10 out of 629 publications