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 vitr o studies of the reaction of carcinogens with purified DNA, in vivo th e DNA is associated with a variety of histone and non-histone proteins in a complex and dynamic structure known as chromatin. The covalent i nteractions of bulky chemical carcinogens with chromatin are reviewed, Differences from bulk genomic DNA in adduct density are found in repl icating, transcribing and nuclear matrix-bound DNA regions, and betwee n DNA in nucleosome cores and linker DNA regions. These differences ra nge from 2- to 3-fold for linker versus core, to similar to 8-fold clo se to a replication fork. Much remains to be done to determine the inf luences of non-histone proteins and higher order chromatin structure o n carcinogen binding.