Preferential binding of the carcinogen benzo[a]pyrene to DNA in active chromatin and the nuclear matrix.
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.
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis; D001483:Base Sequence; D001564:Benzo(a)pyrene / Q000378:metabolism*; D001580:Benzopyrenes / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair; D004261:DNA Replication; D004851:Epoxide Hydrolases / Q000032:analysis; D066298:In Vitro Techniques; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
D001580:Benzopyrenes; D002843:Chromatin; D014316:Tritium; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D004247:DNA; D001189:Aryl Hydrocarbon Hydroxylases; D004851:Epoxide Hydrolases