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The relation of metabolism to macromolecular binding of the carcinogen benzo[ a ]pyrene, by mouse embryo cells in culture
Author(s) -
Duncan Margaret E.,
Brookes P.
Publication year - 1970
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910060321
Subject(s) - metabolism , pyrene , benzo(a)pyrene , macromolecule , carcinogen , embryo , biochemistry , dna , benzopyrene , chemistry , rna , biology , microbiology and biotechnology , organic chemistry , gene
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.