This project's ultimate goal is to identify behavioral and neurochemical indices that provide accessible markers of nervous system injury due to exposure to toxic wastes. The proposed indices (behavioral test of [1] diurnal rhythms and [2] cognitive function and [3] nervous system- specific proteins) can be died both in lab animals and in humans. A 3- tiered approach will be used. First, a practical, noninvasive endpoint (homecage activity of rats) will be used for sub-acute dose range- finding. The purpose is to: 1) develop efficient testing strategies for studies measuring behavior nondestructively and then sharing rats with other, destructive projects; 2) identify model toxicants exhibiting specific neurotoxicity by comparing dose-effect functions with other projects; 3) identify toxicant producing correlated changes in behavior and brain proteins. The dose-effect data will be used in tier 2 to plan longer exposures to the more selective toxicants. Endpoints in rats will be complex, learned behavior similar to that studied in humans, and the proteins found to be most promising in tier 1. The purpose is: 1) to focus on toxicants and exposures which affect the rat's complex, learned behavior; 2) to determine whether the correlated changes in brain proteins can also be detected in rat and human serum; and 3) to obtain normative data on the performance of an objective, nonlingual test of cognitive function for use both with humans and with primates. Tier 3 will: 1) refine the cognitive test of ruse in the field and in clinic; 2) study the cognitive function and correlated proteins in selected populations; and 3) use the human data for planning further experiments aimed at questions that can only be asked with animals. model toxicants will be studied in rats uniformly prepared by the exposure core so as to maximize comparison of results with other projects. Positive neurotoxicants (oral exposure to methlymercury or acrylamide; inhalation of toluene or trichloroethylene) will be contrasted with others though to have less specific neurotoxicity (nickel, chromium, cadmium, benzene, etc.).

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
New York University
New York
United States
Zip Code
Sutherland, J E; Zhitkovich, A; Kluz, T et al. (2000) Rats retain chromium in tissues following chronic ingestion of drinking water containing hexavalent chromium. Biol Trace Elem Res 74:41-53
Corti, M; Snyder, C A (1998) Gender- and age-specific cytotoxic susceptibility to benzene metabolites in vitro. Toxicol Sci 41:42-8
Salnikow, K; Wang, S; Costa, M (1997) Induction of activating transcription factor 1 by nickel and its role as a negative regulator of thrombospondin I gene expression. Cancer Res 57:5060-6
Klein, C B; Costa, M (1997) DNA methylation, heterochromatin and epigenetic carcinogens. Mutat Res 386:163-80
Gong, Z; Evans, H L (1997) Effect of chelation with meso-dimercaptosuccinic acid (DMSA) before and after the appearance of lead-induced neurotoxicity in the rat. Toxicol Appl Pharmacol 144:205-14
Dowjat, W K; Kharatishvili, M; Costa, M (1996) DNA and RNA strand scission by copper, zinc and manganese superoxide dismutases. Biometals 9:327-35
Snyder, C A; Udasin, I; Waterman, S J et al. (1996) Reduced IL-6 levels among individuals in Hudson County, New Jersey, an area contaminated with chromium. Arch Environ Health 51:26-8
Corti, M; Snyder, C A (1996) Influences of gender, development, pregnancy and ethanol consumption on the hematotoxicity of inhaled 10 ppm benzene. Arch Toxicol 70:209-17
Garte, S J; Trachman, J; Crofts, F et al. (1996) Distribution of composite CYP1A1 genotypes in Africans, African-Americans and Caucasians. Hum Hered 46:121-7
Dowjat, W K; Huang, X; Cosentino, S et al. (1996) Peroxidase deficiency of nickel-transformed hamster cells correlates with their increased resistance to cytotoxicity of peroxides. Biometals 9:151-6

Showing the most recent 10 out of 106 publications