Interaction of mineral fibres with lung cytochrome P-450 system: Impairment of drug metabolizing enzyme activities

Abstract

In the present study, in vitro effects of carcinogenic (chrysotile, crocidolite, amosite) and non-carcinogenic (anthophyllite) varieties of asbestos and three varieties of Indian wollastonite (kemolit A-60, Kemolit-N, Kemolit ASB-3) boTh on phase I and phase Ii drug metabolizing enzymes and microsomal lipid peroxidatin (LPO) in rat lung were investigated. All the mineral fibres when incubated with lung microsomes adsorbed cytochrome P-450 to different degrees, while heme was released only by chrysotile and crocidolite. Chrysotile, crocidolite, amosite and kemolit A-60 treatments only led to significant depletion in the activities of benzo(a)pyrene hydroxylase, and epoxide hydratase. The carcinogenic varieties of asbestos also decreased the activity of glutathione-S-transferase, while kemolit-N significantly increased the activity. However, kemolit A-60 and kemolit ASB-3 did not alter the activity of this enzyme. All the dusts which impaired the activities of drug metabolizing enzymes also significantly induced LPO in the microsomes. These data indicate the differential behaviour of asbestos and wollastonite, both on the drug metabolizing enzymes and induction of LPO in rat lung and also suggest that these effects may be related to their toxic potentials.