EFFECT OF COEXPOSURE TO ASBESTOS AND KEROSENE SOOT ON PULMONARY DRUG-METABOLIZING ENZYME-SYSTEM

This article reports the effect of coexposure to Indian chrysotile asb estos (5 mg/rat) and kerosene soot (5 mg/rat) on the pulmonary phase I and phase II drug-metabolizing enzymes 1, 4, 8, 16, 30, 90, and 150 d ays after a single intratracheal inoculation. Exposure to soot resulte d in a significant induction of the pulmonary microsomal cytochrome P4 50 and the activity of dependent monooxygenase, benzo[a]pyrene (B[a]P) hydroxylase, and epoxide hydrase at all time intervals. On the other hand, the cytosolic glutathione S-transferase (GST) activity was induc ed at days 1, 4, 8, 16, and 30 after exposure, followed by inhibition in the enzyme activity. In contrast, chrysotile exposure depleted cyto chrome P450, B[a]P hydroxylase, epoxide hydrase, and GST at initial st ages, while all these parameters except GST were induced at later stag es. However, coexposure to chrysotile and soot led to a significant in hibition in the cytochrome P450 revels, activities of B[a]P hydroxylas e, epoxide hydrase, and GST at initial stages of exposure. At advanced stages, however, an additional increase in cytochrome P450, B[a]P hyd roxylase, and epoxide hydrase but a decrease in GST was observed. Thes e results clearly show that the intratracheal coexposure to high level s of asbestos and kerosene soot alters the metabolic activity of the l ung, which in turn may retain toxins in the system for a longer period , resulting in adverse pathological disorders.