Our research focuses on the metabolic basis of chemical carcinogenesis, with emphasis on tobacco-related lung carcinogenesis. Our hypothesis is that the carcinogenicity of tobacco smoke results from the interactive effects of its chemical constituents, which are present at levels too low for their individual effects to be of significant oncogenic consequence. The target tobacco smoke constituents in our studies include non-polyaromatic hydrocarbons, specifically pyridine and its derivatives, the most abundant of which is nicotine. Ongoing studies include elucidation of the molecular mechanisms by which these compounds and their metabolites, singly and in combinations, regulate the expression of carcinogen-bioactivating enzymes, particularly cytochromes P450 1A (CYP1A and CYP 1A2). We are also examining the influence of the tobacco constituents, CYP 1A expression, and chemopreventive agents on the progression of tobacco carcinogenesis. In vivo (animal and human) models and in vitro experimental systems are used in the studies.

Additional ongoing research includes studies of the metabolic basis of the toxicity and carcinogenicity of organic solvents and aromatic amines.

	Xu X, Iba MM, Weisel C.P., Simultaneous and sensitive determinantion of anabasine, nicotine, and nicotine metabolites in human urine using liquid chromatography/tandem mass spectrometry. Clin. Chem., in press.
	Martin, J.V., Iyer, S.V., McIlroy, P.J. , Iba, M.M. (2004) Influence of oxygenated fuel additives and their metabolites on ?-aminobutyric acidA (GABAA) receptor function in rat brain synaptoneurosomes. Toxicol Letts. 147:209-217.
	Iba, M.M., Ghosal, A., Bennett, S., Reuhl, K.R., Lowndes, H.E. (2003) Constitutive and inducible levels of CYPlAl and CYP1A2 in rat cerebral cortex and cerebellum. Arch. Toxicol. 77:547-554.
	Wei C, Caccavale RJ, Weyand EH, Chen S, Iba MM. (2002) Induction of CYP1A1 and CYP1A2 expression by prototypic and atypical inducers in the human lung. Cancer Letts. 178:25-36.