This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Exposure to atrazine, one of the widely used herbicides in the United States, has been associated with deleterious effects on various organ systems. However, in order to establish the human health relevancy of these studies, tissue dosimetry and pharmacokinetics studies are needed. In addition, atrazine metabolism is dependent in large measure upon the activities of cytochrome P450 (CYP) mono-oxygenases. Certain pesticides that are now banned, but still widely present in the environment, such as the insecticide dieldrin, are known CYP inducers. The persistence of dieldrin and the high use of atrazine, increase the likelihood of exposure to these two pesticides in combination. Existing analytical methods to analyze atrazine in biological matrices have various drawbacks. We have recently developed an LC-MS method to analyze atrazine and all of its major mammalian metabolites in mouse plasma and urine. In this project, we will optimize this method for determination of atrazine and its metabolites in target tissues and then use it to determine how atrazine s tissue disposition and pharmacokinetics are influenced by prior or concurrent dieldrin exposure. Our long-term goal is to understand better how the pharmacokinetics and tissue distribution of environmentally-relevant pesticides changes when organisms are exposed to pesticide mixtures. More specifically, we will determine whether prior/ongoing exposure to dieldrin will alter atrazine s pharmacokinetics. When completed, this research is expected to not only delineate the effects of dieldrin exposure on the pharmacokinetics of atrazine, but to also underscore the importance of pesticide interaction in risk assessment.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR017661-05
Application #
7381819
Study Section
Special Emphasis Panel (ZRR1-RI-A (02))
Project Start
2006-07-01
Project End
2007-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
5
Fiscal Year
2006
Total Cost
$35,721
Indirect Cost
Name
Mississippi State University
Department
Public Health & Prev Medicine
Type
Schools of Veterinary Medicine
DUNS #
075461814
City
Mississippi State
State
MS
Country
United States
Zip Code
39762
Hossain, Delwar; Pittman Jr, Charles U; Gwaltney, Steven R (2014) Structures and Stabilities of the Metal Doped Gold Nano-Clusters: M@Au10 (M = W, Mo, Ru, Co). J Inorg Organomet Polym Mater 24:241-249
Ross, Matthew K; Borazjani, Abdolsamad; Wang, Ran et al. (2012) Examination of the carboxylesterase phenotype in human liver. Arch Biochem Biophys 522:44-56
Yu, Xiaozhen; Sigler, Sara C; Hossain, Delwar et al. (2012) Global and local molecular dynamics of a bacterial carboxylesterase provide insight into its catalytic mechanism. J Mol Model 18:2869-83
Carr, Russell L; Borazjani, Abdolsamad; Ross, Matthew K (2011) Effect of developmental chlorpyrifos exposure, on endocannabinoid metabolizing enzymes, in the brain of juvenile rats. Toxicol Sci 122:112-20
Howell 3rd, George; Mangum, Lauren (2011) Exposure to bioaccumulative organochlorine compounds alters adipogenesis, fatty acid uptake, and adipokine production in NIH3T3-L1 cells. Toxicol In Vitro 25:394-402
Crow, J Allen; Herring, Katye L; Xie, Shuqi et al. (2010) Inhibition of carboxylesterase activity of THP1 monocytes/macrophages and recombinant human carboxylesterase 1 by oxysterols and fatty acids. Biochim Biophys Acta 1801:31-41
Eells, Jeffrey B; Brown, Timothy (2009) Repeated developmental exposure to chlorpyrifos and methyl parathion causes persistent alterations in nicotinic acetylcholine subunit mRNA expression with chlorpyrifos altering dopamine metabolite levels. Neurotoxicol Teratol 31:98-103
Johnson, Frank O; Chambers, Janice E; Nail, Carole A et al. (2009) Developmental chlorpyrifos and methyl parathion exposure alters radial-arm maze performance in juvenile and adult rats. Toxicol Sci 109:132-42
Carr, Russell L; Nail, Carole A (2008) Effect of different administration paradigms on cholinesterase inhibition following repeated chlorpyrifos exposure in late preweanling rats. Toxicol Sci 106:186-92
Moore, Talisha M; Brown, Timothy; Cade, Mirae et al. (2008) Alterations in amphetamine-stimulated dopamine overflow due to the Nurr1-null heterozygous genotype and postweaning isolation. Synapse 62:764-74

Showing the most recent 10 out of 31 publications