Robert A. SchatzAssociate Professor
Director Toxicology Program
Office: 314 Mugar Hall
Ph.D., University of Rhode Island
M.S., Northeastern University
B.S., Massachusetts College of Pharmacy
Registered Pharmacist in MA
Regulation of Drug Metabolism
Major Research Areas
The toxicologic effects of exposure to mixtures of chemicals is an important, relatively unexplored area of environmental and occupational concern. Our laboratory is interested in the effects of combined solvent (toluene, xylenes) inhalation exposure on the regulation of cytochrome P450 drug metabolizing systems in the respiratory tract (lung, nasal mucosa). Exposure to these solvents has been shown to shift the metabolism of the polyaromatic hydrocarbon (PAH) carcinogen benzo(a)pyrene towards formation of more carcinogenic (bay-region diol) metabolites. These metabolites have the ability to bind to DNA thus initiating the carcinogenic process raising the possibility that individuals who are concurrently exposed to aromatic solvents and PAHs may be at greater risk of cancer. Conversely, in other co-exposure scenarios, decreased respiratory toxicity (determined by lavage fluid analyses and histology) have been observed. For example, ethylbenzene (gasoline additive) co-exposure prevented styrene-induced respiratory toxicity. Both agents are used in polystyrene production. Xylene co-exposure also decreased the toxicity of 1-nitonaphthalene (PAH) as well as MTBE (fuel oxygenate). The ability of low-level solvent exposure to organ-selectively alter CYP450 isozyme activities and subsequent respiratory toxicity has potential implications for risk-assessment of co-exposure scenarios.
Park, S.H. and Schatz, R.A.: Effect of low-level short term o-xylene inhalation on benzo(a)pyrene (BaP) metabolism and BaP-DNA adduct formation in rat liver and lung microsomes. Journal of Toxicology and Environmental Health 58: 101-114, 1999.
Vaidynathan, A., Foy, J.W.-D. and Schatz, R.A. Inhibition of rat respiratory-tract cytochrome P-450 isozymes following inhalation of m-xylene: Possible role of metabolites. Journal of Toxicology and Environmental Health 66: 1133-1143, 2003.
Foy, J.W.-D. and Schatz. R.A. Inhibition of rat respiratory tract cytochrome P450 activity after low-level m-xylene inhalation: Role in 1-nitronaphthlene toxicity. Inhalation Toxicology 16: 1-8, 2004. (in press)