Environmental carcinogens of the polynuclear aromatic hydrocarbon class such as benzo(a)pyrene are metabolized by cellular enzyme systems to highly reactive bay region diol epoxides which have been identified as ultimate carcinogens. In addition to modifying DNA, these electrophiles bind covalently to proteins which are involved in chromatin structure. In particular, the ultimate carcinogen derived from B(a)P, B(a)P diol epoxide-I (BPDE-I) binds specifically to histones H3 and H2A in intact nuclei, intact cells and in purified chromatin. We have very little information concerning the effects of such protein lesions on the structure and function of chromatin, effects which could be important in the process of carcinogenesis. We propose to extend our structural studies of this binding reaction to the point where we can position the target sites in the three-dimensional structure of the nucleosome. We will determine structural changes in nucleosomes induced by these adducts and we will use an in vitro, eucaryotic transcription system to look for functional changes which may accompany histone modification. We will also begin to study the effects of BPDE-I on the transcriptional control system which involves the 5S-RNA genes, the 5S transcripts and a positive transcriptional factor, TFIIIA.