The metabolism of benzo(a)pyrene in rat liver microsomes: The effect of asbestos-associated metal ions and pH

Abstract

Experimental evidence is presented to support the hypothesis that trace metals and other factors associated with asbestos mined in different areas play a more critical role in the development of “asbestos tumours” than the actual fibre itself. In vitro experiments were performed to investigate the effect of these associated factors on the metabolism of benzo( a)pyrene, a carcinogen introduced into the lung as a result of smoking and atmospheric pollution. The amount of benzo( a)pyrene metabolized by the enzyme in rat liver microsomes was measured in the presence of increasing amounts of trace metal ions. Copper, zinc, lead, nickel, chromium, ferrous, ferric, and magnesium ions were found to inhibit enzyme activity to an increasing extent as their concentration increased; manganese was an exception in that it activated the enzyme at lower concentrations and inhibited it at higher concentrations. Enzyme activity was also considerably affected by changes in pH, with a great loss of activity at the high pH values measured for aqueous suspensions of crocidolite and chrysotile. The effect of manganese ions differed at various pH values, the enzyme-activating effect of these ions being restricted to a much smaller concentration range at a high pH.