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 distributionof DNA adducts generated by the chemical carcinogen r-7, t-8-dihydroxy-t-9,10-oxy-7, 8, 9, 10-tetrahydrobenzo[a]pyrene (BPDE). Treatmentof mouse embryo cells with BPDE results in 3.5 times more bindingto the linker DNA regions between nucleosome cores than to thenucleosome core DNA itself, but 24 h post-treatment incubationof these cells leads to a loss of this non-random binding. Asimilar result was obtained when post-treatment incubation wascarried out in the presence of hydroxyurea indicating that factorsother than DNA replication are responsible for this change inadduct distribution. However in the case of excision repairdeficient xeroderma pigmentosum (XP12/BE) cells the non-randomadduct distribution was stable over a period of 48 h, whereaswith excision repair proficient XP variant (XP4/BE) cells, lossof preferential binding did occur. These results indicate thatthe loss of non-random nucleosomal DNA modification with timecan be accounted for by the preferential removal of adductsfrom micrococcal nuclease sensitive linker DNA and further,demonstrates that in certain cells at least, the relative positionof nucleosome core structures on DNA remains unchanged overa period of at least 48 h.