Abstract 615: Knock-down of base excision repair genes increases susceptibility to organophospate pesticide toxicity

• Published in: Cancer research (Chicago, Ill.) Vol. 73; no. 8_Supplement; p. 615
• Main Authors: Saulsbury, Marilyn D., Heyliger, Simone, Li, Feng, Parker-Johnson, KiTani A.
• Format: Journal Article
• Language: English
• Published: 15.04.2013
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2013-615

Abstract Organophosphates are chemicals that inhibit cholinesterases and are employed widely as pesticides. Concerns are increasing regarding the relative safety of these chemicals to the environment. Recent studies suggest organophosphate exposure is associated with increased expression of fragile sites and DNA damage at concentrations that are not associated with cholinesterase inhibition. Chronic exposure to the organophosphate has been associated with high incidences of prostate cancer in farm workers as well as leukemia and non-Hodgkin lymphoma in adults and children. Moreover, a higher degree of DNA damage has been reported in pesticide applicators that have polymorphisms in the base excision repair genes XRCC1 and OGG1. Our laboratory reports that cells deficient in BER enzymes APE1 and OGG1 exhibit a higher cytotoxicity when exposed, in a dose-dependent manner, to organophosphates Chlorpyrifos, Chlorpyrifos-oxon and Isofenphos. However, it should be noted that other organophosphates such as Diazinon and Dichlorvos had very little effects on cellular viability within the APE1 and OGG1 deficient cells. It should be noted that Chlorpyrifos, Chlorpyrifos-oxon and Isofenphos also produce significant oxidative stress in cells. Our data is consistent with previous studies which report a higher degree of DNA damage has been reported in pesticide applicators that have polymorphisms in the base excision repair genes XRCC1 and OGG1. Moreover, our data further suggests that only certain organophosphates, particularly those that induce oxidative stress, may be responsible for toxicity in APE1 and OGG1 deficient cells. Citation Format: Marilyn D. Saulsbury, Simone Heyliger, Feng Li, KiTani A. Parker-Johnson. Knock-down of base excision repair genes increases susceptibility to organophospate pesticide toxicity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 615. doi:10.1158/1538-7445.AM2013-615