A note on the interaction of carcinogenic molecules with cellular protein.

A hypothesis formulated by Otto Schmidt (21) to account for the carcinogenic activity of chemical substances has been widely exploited during the last 15 years (for review see [19]). The theory is based on the assumption that a very important step in the production of a cancer is an interaction between cellular constitu ents and a zone of the hydrocarbon which is par ticularly rich in it electrons. The proposal of Schmidt has received confirma tion from two kinds of investigations. On the one hand, the complex between carcinogenic sub stance and proteins has been demonstrated experi mentally (1, 10, 11, 13, 14, 23). On the other hand, theoretical investigations have shown, for example, that there is a parallel between the electronic charge of a certain region of angular benzacridine derivatives and the carcinogenic ac tivity of these molecules (4, 19). Since carcinogenic molecules in general have a bond with a high bond order (5, 19) (which is often called the K region) (19), it has seemed reasonable to suppose that a necessary condition for an aromatic derivative to be carcinogenic is that it have a strong tendency to add to cellular proteins by one of its bonds. However, Woodhouse (24) has shown that certain noncarcinogenic hy drocarbons are also fixed on tissue. Thus, perhaps the formation of the complex is not as important as the kind of complex which is formed (15). As the nature of the complex is a problem which is very difficult to investigate experimentally, we propose in this paper to suggest from theoretical considerations different possibilities which may be then correlated with biological activity.