INTERACTION OF BULKY CHEMICAL CARCINOGENS WITH DNA IN CHROMATIN

DNA damage is an important effect of treatment of cells and organisms with chemical carcinogens. Although much has been learned from in vitro studies of the reaction of carcinogens with purified DNA, in vivo the DNA is associated with a variety of histone and non-histone proteins in a complex and dynamic structure known as chromatin. The covalent interactions of bulky chemical carcinogens with chromatin are reviewed, Differences from bulk genomic DNA in adduct density are found in replicating, transcribing and nuclear matrix-bound DNA regions, and between DNA in nucleosome cores and linker DNA regions. These differences range from 2- to 3-fold for linker versus core, to similar to 8-fold close to a replication fork. Much remains to be done to determine the influences of non-histone proteins and higher order chromatin structure on carcinogen binding.