This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Naphthalene is a volatile hydrocarbon which causes dose, species and cell type dependent cytotoxicity after acute exposure and hyperplasia/neoplasia after lifetime exposures in rodents. Toxicity depends upon metabolic activation, and reactive metabolite protein binding correlates with tissue and site susceptibility. Human exposure to naphthalene is universal and occurs from a variety of combustion-related sources but epidemiologic evidence for health effects of human exposure are lacking. Comparative studies examining processes thought to be essential to the toxicity of naphthalene have been examined in nasal epithelium of rats and Rhesus macaques. The studies currently being conducted are focused on determining the kinetics for the initial step in naphthalene metabolism in microsomes prepared from susceptible (rat and mouse nasal olfactory epithelium, mouse airways) and non target (rat airways) tissues in comparison to non-human primates. The highest rates of substrate turnover were in the rat nasal olfactory epithelium (30 nmoles/mg/min). Rates of metabolism in mouse olfactory microsomes (16.4) were half those in the rat. Microsomes from monkey nasoturbinates were less than 10% those of the mouse. Microsomes from dissected murine airways catalyzed NA metabolism at 10.9 nmole/mg/min whereas metabolism in rat airways occurred at 5% of this rate. The majority of the metabolites were accounted for as GSH conjugates of the 1,2-epoxide. At longer incubation times diGSH conjugates of the diepoxide and GSH adducts of the diol epoxide and 1,4-naphthoquinone were observed in all preparations except rat airway. Under the conditions used, less than 12% of the total metabolites produced were accounted for by 1-naphthol or dihydrodiol. Microsomes from mouse airways, mouse and rat nasal olfactory epithelium showed a high degree of stereoselectivity in NA epoxidation (20:1), rat airways and monkey nasal samples did not. Tissue susceptibility to NA-induced injury correlates with high rates of substrate turnover;metabolism in the nasal epithelium of monkeys is 10-50 fold lower than in rat olfactory epithelium.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000169-50
Application #
8357260
Study Section
Special Emphasis Panel (ZRR1-CM-5 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
50
Fiscal Year
2011
Total Cost
$25,210
Indirect Cost
Name
University of California Davis
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Han, Pengcheng; Nielsen, Megan; Song, Melissa et al. (2017) The Impact of Aging on Brain Pituitary Adenylate Cyclase Activating Polypeptide, Pathology and Cognition in Mice and Rhesus Macaques. Front Aging Neurosci 9:180
Pittet, Florent; Johnson, Crystal; Hinde, Katie (2017) Age at reproductive debut: Developmental predictors and consequences for lactation, infant mass, and subsequent reproduction in rhesus macaques (Macaca mulatta). Am J Phys Anthropol 164:457-476
Zhang, Xinjun; Kanthaswamy, Sree; Trask, Jessica S et al. (2017) Genetic Characterization of a Captive Colony of Pigtailed Macaques (Macaca nemestrina). J Am Assoc Lab Anim Sci 56:390-395
Jensen, Kara; Dela Pena-Ponce, Myra Grace; Piatak Jr, Michael et al. (2017) Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine. Clin Vaccine Immunol 24:
Rose, Destanie R; Careaga, Milo; Van de Water, Judy et al. (2017) Long-term altered immune responses following fetal priming in a non-human primate model of maternal immune activation. Brain Behav Immun 63:60-70
Hasan, M Kamrul; Feeroz, M Mostafa; Jones-Engel, Lisa et al. (2016) Performing monkeys of Bangladesh: characterizing their source and genetic variation. Primates 57:221-30
Austin, Christine; Smith, Tanya M; Farahani, Ramin M Z et al. (2016) Uncovering system-specific stress signatures in primate teeth with multimodal imaging. Sci Rep 6:18802
Scott, Julia A; Grayson, David; Fletcher, Evan et al. (2016) Longitudinal analysis of the developing rhesus monkey brain using magnetic resonance imaging: birth to adulthood. Brain Struct Funct 221:2847-71
Rueda, Cesar M; Presicce, Pietro; Jackson, Courtney M et al. (2016) Lipopolysaccharide-Induced Chorioamnionitis Promotes IL-1-Dependent Inflammatory FOXP3+ CD4+ T Cells in the Fetal Rhesus Macaque. J Immunol 196:3706-15
Bliss-Moreau, Eliza; Moadab, Gilda (2016) Variation in Behavioral Reactivity Is Associated with Cooperative Restraint Training Efficiency. J Am Assoc Lab Anim Sci 55:41-9

Showing the most recent 10 out of 393 publications