The objectives of the research are to: a. characterize changes in exhaled breath volatile organic compounds (Voce) of the F344/N rat resulting from either induction or inhibition of specific cytochrome P450 isoforms, b. evaluate changes in VOCs resulting from inhibition or induction of enzymes involved in steroid synthesis, c. evaluate VOC changes resulting from depletion of tissue glutathione. Prior work has demonstrated a consistent pattern of approximately 70 detectable VOCs from normal expired rat breath collected on Tenax sorbant. Inhibition of cytochrome P450s by a non selective irreversible inhibitor, aminobenzotriazole, resulted in a dramatic increase in the quantity and number of exhaled components. This has led to the proposed studies which will attempt to determine if exogenous exhaled compounds might be used as biomarkers for a particular P450 phenotype. Prior studies have also shown gender related differences in breath components. Modulation of sex steroid synthesis and/or castration or ovariectomy may result in breath changes. Optional studies include possible development and characterization of a breath collection and analysis system for the B6C3F1 mouse.
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| Mathews, J M; Raymer, J H; Etheridge, A S et al. (1997) Do endogenous volatile organic chemicals measured in breath reflect and maintain CYP2E1 levels in vivo? Toxicol Appl Pharmacol 146:255-60 |
