Hepatic enzyme induction and mutagenicity of airborne particulate matter from Santiago, Chile in the nourished and malnourished rat

Abstract

1. Respirable, airborne particles in the ambient air in downtown Santiago, Chile, have been characterized for the seasonal variation in total polycyclic aromatic hydrocarbon content, 13 of which have been identi® ed including the mutagens (benzo(a)pyrene, dibenzo(a,h)anthracene, benzo(a)anthracene, benzo(b)¯ uoranthene and indeno(1,2,3, c,d)pyrene amongst others. 2. Organic extracts derived from these particles were administered to both the nourished and malnourished rat and resulted in modulation of the hepatic mixed function oxidase system including induction of NADPH-cytochrome P450 reductase, cytochrome P4501A as determined by Western blot analysis and the associated ethoxyresoru® n Odeethylase and aryl hydrocarbon hydroxylase activities. 3. The cytochrome P4504A1-dependent 12-hydroxylation of lauric acid was induced in the malnourished state, but this activity was signi® cantly inhibited by treatment of the animals with particle extracts in both nutritional states. 4. The particle extracts contained both direct and indirect-acting mutagens in the Ames test, and depending on the relative complement of both, resulted in either increased or decreased mutagenicity in the presence of S9 activation systems derived from both nourished and malnourished animals. 5. These results are discussed in the context of the interindividual risk assessment of airborne, particulate matter to man.