The proposed studies aim to develop high throughput protocols for assessing OP exposures by characterizing specific biomarker proteins in blood, and to make use of these more accurate measures of exposure to investigate gene/environment interactions related to genetic variability in the paraoxonase (PONI) gene, particularly with respect to OP exposures that occur during early development.
Specific Aim 1 is to validate high throughput immunomagnetic bead (1MB) based isolation protocols for rapid purification and analysis of the active site peptides of two proteins, red cell acyl peptide hydrolase (APH) and plasma butyrylcholinesterase (BChE), as biomarkers of exposure to OP compounds. A targeted proteomics strategy based on microcapillary liquid chromatography-selected reaction monitoring-mass spectrometry (?mu?LC-SRM-MS) will be validated and used to quantify the percentage modification of BChE and APH in archived samples from the Community Based Participatory Research Project. Data from the biomarker experiments will be correlated with other data available on urinary metabolite levels, inhibition of APH and/or BChE, and PONI status.
Specific Aims 2 and 3 use knockout and humanized mouse models to determine the importance of PONI status for OP exposures that occur during critical periods of early development.
Specific Aim 2 is to determine the extent to which APH and BChE are covalently modified following test exposure of pregnant mice to chlorpyrifos (CP) or CPO.
Specific Aim 3 is to determine the extent to which BChE and APH are covalently modified following exposure of neonatal mice to CP or CPO.
These aims will evaluate interactions among biomarkers of sensitivity, exposure and response in an in vivo system, allowing us to determine full dose responses of the OP compounds and generate quantitative biomarker data.
These experiments will integrate the the interactions among biomarkers of susceptibility, exposure, and response to OP compounds during critical periods of development. Using MS analysis of modified APH and BChE to examine the role of genetic variability of P0N1 in modulating gene environment interactions will provide a more detailed understanding of the role of P0N1 in modulating environmental exposures to OPs.
|Wegner, Susanna H; Yu, Xiaozhong; Pacheco Shubin, Sara et al. (2015) Stage-specific signaling pathways during murine testis development and spermatogenesis: A pathway-based analysis to quantify developmental dynamics. Reprod Toxicol 51:31-9|
|Thompson, Beti; Griffith, William C; Barr, Dana B et al. (2014) Variability in the take-home pathway: farmworkers and non-farmworkers and their children. J Expo Sci Environ Epidemiol 24:522-31|
|Hohl, Sarah D; Gonzalez, Claire; Carosso, Elizabeth et al. (2014) "I did it for us and I would do it again": perspectives of rural latinos on providing biospecimens for research. Am J Public Health 104:911-6|
|Pizzurro, Daniella M; Dao, Khoi; Costa, Lucio G (2014) Astrocytes protect against diazinon- and diazoxon-induced inhibition of neurite outgrowth by regulating neuronal glutathione. Toxicology 318:59-68|
|Smith, Marissa N; Griffith, William C; Beresford, Shirley A A et al. (2014) Using a biokinetic model to quantify and optimize cortisol measurements for acute and chronic environmental stress exposure during pregnancy. J Expo Sci Environ Epidemiol 24:510-6|
|Pizzurro, Daniella M; Dao, Khoi; Costa, Lucio G (2014) Diazinon and diazoxon impair the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons. Toxicol Appl Pharmacol 274:372-82|
|Armstrong, Jenna L; Dills, Russell L; Yu, Jianbo et al. (2014) A sensitive LC-MS/MS method for measurement of organophosphorus pesticides and their oxygen analogs in air sampling matrices. J Environ Sci Health B 49:102-8|
|Shepherd-Banigan, Megan; Ulrich, Angela; Thompson, Beti (2014) Macro-activity patterns of farmworker and non-farmworker children living in an agricultural community. Environ Res 132:176-81|
|Roqué, Pamela J; Guizzetti, Marina; Costa, Lucio G (2014) Synaptic structure quantification in cultured neurons. Curr Protoc Toxicol 60:12.22.1-12.22.32|
|Marsillach, Judit; Costa, Lucio G; Furlong, Clement E (2013) Protein adducts as biomarkers of exposure to organophosphorus compounds. Toxicology 307:46-54|
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