The mechanism of carcinogenesis by polycyclic hydrocarbons is one of the important problems of cancer research. The evidence points to the occurrence of active olefinic """"""""K-regions"""""""" and """"""""bay regions"""""""" that are primarily responsible for the carcinogenetic potential of certain benzenoid compounds. Enzymatic oxidation of such reactive sites to provide potentially alkylating epoxides and diol epoxides is thought to be one of the crucial events occurring in the conversion of aromatic hydrocarbons to carcinogens. However, the necessary requirements for carcinogenic action in polycyclic hydrocarbons is ill-understood. In particular, it is not clear to what extent topology and electronic structure play a role in carcinogenic potential. To elucidate this point, the synthesis of novel polycyclic hydrocarbons fused to or incorporating activating rings is proposed, to enable the study of their physical and chemical properties. The activating ability of such rings will be related to their electronic make up and the effect of in and out-of-plane strain. In larger systems, fusion will be designed such as to activate remote K-regions and bay regions of known carcinogens. Novel synthetic routes developed in the principal investigators laboratory will be applied to attain this goal. The new hydrocarbons are being made available for physiological testing. The carcinogenic and mutagenic potential of these new compounds will be compared with the activity of known systems.
