Preferential binding of the carcinogen benzo[a]pyrene to DNA in active chromatin and the nuclear matrix |
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Authors: | Obi, F.O. Ryan, A.J. Billett, M.A. |
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Affiliation: | Department of Biochemistry, University of Nottingham Medical School, Queen's Medical Centre Nottingham NG7 2UH, UK |
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Abstract: | Rat liver nuclei or hepatocytes were incubated with the proximatecarcinogen, benzo[a]pyrene (BP) and its ultimate carcinogen,anti-benzo[a]pyrene-7, 8-dol-9,10-epoxide (BPDE. Following carcinogenexposure, nuclei were fractionated by micrococcal nuclease digestionand stepwise extraction to yield an active chromatin fractionenriched in transcribed versus non-transcribed genes, a bulkchromatin fraction, a high-salt-extracted chromatin fractionand a nuclear matrix fraction containing elevated concentrationsof transcribed and non-transcribed genes. BP binds more readilyto DNA of active chromatin and nuclear matrix than to bulk chromatin.Since low concentrations of BPDE also selectively damage activechromatin and matrix DNA, selectivity is not due to the sub-nuclearlocation of enzymes which activate BP to BPDE. Higher BPDE concentrationscause more uniform DNA damage. Selective carcinogen attack mayresult from an accessible DNA conformation in active chromatinand matrix or from partitioning of carcinogen in the nuclearmembrane. |
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