Chemical Constitution and Carcinogenic Activity

Abstract

Publisher Summary The study of chemical carcinogenesis dates from 1915, when cancer was first produced experimentally by the long-continued application of coal tar to the ears of rabbits, but it was not until 1930 that cancer was produced by the application of a pure polycyclic aromatic hydrocarbon, 1,2,5,6-dibenzanthracene, to the skin of mice. It is commonplace in all studies of the relation between chemical constitution and biological action that the same biological end result can frequently be brought about by different classes of chemical compounds acting by different mechanisms. Complex formation only occurs with molecules of suitable molecular complexity, and it is prevented by large substituents and by the presence of substituents in certain parts of the molecule; it does not occur if the molecule is buckled by hydrogenation. Complex formation is greatly facilitated by the presence of an activated K region, but the necessary degree of activation may vary considerably, depending on the molecular complexity. The carcinogenic azo compounds enter into some form of complex with a cellular receptor so that the factors that influence the ease of formation and stability of such a complex may well be of importance. The electron density of the K region may be a controlling factor, but large substituents may offer steric hindrance to the formation of the complex.