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Rat liver nuclei or hepatocytes were incubated with the proximate carcinogen, benzo[a]pyrene (BP) and its ultimate carcinogen, anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE). Following carcinogen exposure, nuclei were fractionated by micrococcal nuclease digestion and stepwise extraction to yield an active chromatin fraction enriched in transcribed versus non-transcribed genes, a bulk chromatin fraction, a high-salt-extracted chromatin fraction and a nuclear matrix fraction containing elevated concentrations of transcribed and nontranscribed genes. BP binds more readily to DNA of active chromatin and nuclear matrix than to bulk chromatin. Since low concentrations of BPDE also selectively damage active chromatin and matrix DNA, selectivity is not due to the subnuclear location of enzymes which activate BP to BPDE. Higher BPDE concentrations cause more uniform DNA damage. Selective carcinogen attack may result from an accessible DNA conformation in active chromatin and matrix or from partitioning of carcinogen in the nuclear membrane.

Original publication

DOI

10.1093/carcin/7.6.907

Type

Journal article

Journal

Carcinogenesis

Publication Date

06/1986

Volume

7

Pages

907 - 913

Keywords

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide, Animals, Aryl Hydrocarbon Hydroxylases, Base Sequence, Benzo(a)pyrene, Benzopyrenes, Cell Nucleus, Chromatin, DNA, DNA Repair, DNA Replication, Epoxide Hydrolases, In Vitro Techniques, Rats, Rats, Inbred Strains, Tritium