The relation of metabolism to macromolecular binding of the carcinogen benzo[a]pyrene, by mouse embryo cells in culture

Abstract The metabolism of tritiated benzo[a]pyrene (B[a]P) by primary mouse embryo cells in culture was studied. At concentrations of B[a]P in the medium below about 2–3 mμ moles/ml, metabolism was exponential with time, but at higher concentrations a period of rapid metabolism was followed by a progressive decline. The extent of binding of the hydrocarbon to DNA, RNA and protein was studied under the above conditions. It was found that at low doses of hydrocarbon the binding to macromolecules was proportional to the overall metabolism, with the result that the binding index, i.e. the amount of hydrocarbon bound divided by the amount metabolized, was constant. At higher dose levels, overall metabolism did increase with dose whereas macromolecular binding reached a plateau value. This resulted in a fall in the “binding index” below the constant value found at low doses of B[a]P. As a consequence of these results and those of other workers, a model scheme is proposed for the enzymic metabolism of B[a]P which accords with the known facts of metabolism and macromolecular binding.