Mechanism for the loss of preferential benzo [a] pyrene binding to the linker DNA of chromatin.
We have examined the fate of the asymmetric chromosomal distribution of DNA adducts generated by the chemical carcinogen r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPDE). Treatment of mouse embryo cells with BPDE results in 3.5 times more binding to the linker DNA regions between nucleosome cores than to the nucleosome core DNA itself, but 24 h post-treatment incubation of these cells leads to a loss of this non-random binding. A similar result was obtained when post-treatment incubation was carried out in the presence of hydroxyurea indicating that factors other than DNA replication are responsible for this changes in adduct distribution. However in the case of excision repair deficient xeroderma pigmentosum (XP12/BE) cells the non-random adduct distribution was stable over a period of 48 h, whereas with excision repair proficient XP variant (XP4/BE cells, loss of preferential binding did occur. There results indicate that the loss of non-random nucleosomal DNA modification with time can be accounted for by the preferential removal of adducts from micrococcal nuclease sensitive linker DNA and further, demonstrates that in certain cells at least, the relative position of nucleosome core structures on DNA remains unchanged over a period of at least 48 h.
D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D004247:DNA / Q000032:analysis / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D006918:Hydroxyurea / Q000494:pharmacology; D051379:Mice; D008836:Micrococcal Nuclease; D009707:Nucleosomes / Q000378:metabolism; D014983:Xeroderma Pigmentosum
D001580:Benzopyrenes; D002843:Chromatin; D009707:Nucleosomes; D001564:Benzo(a)pyrene; D004247:DNA; D008836:Micrococcal Nuclease; D006918:Hydroxyurea