Environmental toxins have been shown to induce genotoxic and genome-destabilizing DNA lesions that must be repaired to prevent oncogenesis. Recently, concerns have arisen regarding the relative safety of organophosphate pesticides to the environment. Organophosphate residues are found in human blood and urine samples, livestock, avian species, soil samples, drinking water and foods for human consumption. Chronic exposure to pesticides, including organophosphates, leads to an increased incidence of DNA damage and chromosomal alterations, suggesting that pesticides may act as environmental carcinogens. This pilot project will therefore study genomic instability induced by the organophosphate Isofenphos (IFF). Chronic IFF poisoning has been linked to myeloid metaplasia and acute myelogenous leukemia. Such oncogenic properties likely stem from IFF induced chromosomal aberrations observed in human lymphocytes. Here we propose to extend these observations by determining putative mechanism(s) utilized by IFF to induce chromosomal damage and create genomic instability in lymphocytes. In addition, we will identify DNA repair systems likely to be involved in reversing IFP-induced DNA damage and define the DNA damage response pathways that mediate the cellular reaction to pesticide exposure. Relevance: This pilot project will converge the toxicology expertise of Dr. Heyliger and the DNA damage and repair expertise of Dr. Sobol to dissect mechanisms associated with toxicity and carcinogenicity associated with environmental toxicants such as isophenfos.
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| Kothandapani, Anbarasi; Sawant, Akshada; Dangeti, Venkata Srinivas Mohan Nimai et al. (2013) Epistatic role of base excision repair and mismatch repair pathways in mediating cisplatin cytotoxicity. Nucleic Acids Res 41:7332-43 |
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| Dallal, Cher; Garte, Seymour; Ragin, Camille et al. (2013) Plasma leptin levels, LEPR Q223R polymorphism and mammographic breast density: a cross-sectional study. Int J Biol Markers 28:161-7 |
| Taioli, Emanuela; Sears, Vestra; Watson, Alexis et al. (2013) Polymorphisms in CYP17 and CYP3A4 and prostate cancer in men of African descent. Prostate 73:668-76 |
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| Kothandapani, Anbarasi; Dangeti, Venkata Srinivas Mohan Nimai; Brown, Ashley R et al. (2011) Novel role of base excision repair in mediating cisplatin cytotoxicity. J Biol Chem 286:14564-74 |
| Ragin, Camille C; Langevin, Scott M; Marzouk, Mark et al. (2011) Determinants of head and neck cancer survival by race. Head Neck 33:1092-8 |
| Lisovich, Alex; Chandran, Uma R; Lyons-Weiler, Maureen A et al. (2011) A novel SNP analysis method to detect copy number alterations with an unbiased reference signal directly from tumor samples. BMC Med Genomics 4:14 |
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