Retardation of the Rate of Tumor Induction by Hydrolyzing Chlor-Compounds

The effect on the rate of tumor induction of a group of chlor-compounds which reversibly inhibit the glycolyric process of cells has already been described (5, 6). The compounds used were soluble in water and fats, and were nonhydrolyzable under physiological conditions of pH and temperature. The chemical reactivity of their chlorine atoms was the factor which determined the potency of their biological action. But their influence on tumor induction was not simple. Inhibitory or stimulatory effects could be obtained by a single chlor-compound, the final result being determined by the concentration used and also by the time of its application relative to the treatment with carcinogen. The most active nonhydrolyzing chlor-compound used was mono-chloracetone. It would have been possible to study the effects of still more active halogen compounds of this type; e.g., the bromine and iodine analogues of mono-chloracetone, had not the irritating properties of such compounds precluded their use. Chlor-compounds, considered from the point of view of increasing chemical reactivity, can be ranged from the nonhydrolyzing types used in the earlier work to types which are so reactive that contact with aqueous media causes hydrolysis. The acid chlorides are familiar examples of this type, and they can be graded according to their rate of hydrolysis. Berenblum (>3) has focused attention on mustard gas and related compounds which come under the heading of hydrolyzing halogen compounds. In the work reported here, a series of aliphatic, and one aromatic, acid chlorides has been used. The experiments demonstrate that all these acid chlorides exert an inhibiting influence on the process of tumor induction in the skin of mice by 3,4-benzpyrene. The degree of inhibition by the different members of this class of compounds varies with their physical and chemical characteristics, molecular size and rate of hydrolysis being the variable factors which probably determine their relative effectiveness.