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A Comparison of the Biologic Activities and of the Chemical Properties of Chlorambucil and Trenimon¹

Manitoba Cancer Foundation, and the Department of Anatomy and Internal Medicine, University of Manitoba, Winnipeg 3, Manitoba, Canada

Chlorambucil and Trenimon are alkylating agents which are in current clinical use for the treatment of malignant diseases. A comparison of their biologic action on V79-1 Chinese hamster cells growing in vitro, was made by measurement of division delay and of the loss of colony-forming ability. With respect to division delay, the qualitative response of the two compounds is similar, but the ratio of the doses for the same quantitative effect is 4000 of Chlorambucil to 1 of Trenimon. With respect to loss of colony-forming ability, a similar large difference was observed in the sensitivity of the cells to the two compounds. A study was made of the effect of pH on the fat solubility of the compounds and on their chemical reactivity. The ability of these two compounds to combine with protein and to interact with red blood cells also has been investigated. The results suggest that the large quantitative difference between the biologic actions of the two compounds is a reflection of the relative abilities of the two compounds to penetrate the cell under the conditions of cell culture which prevailed.

¹ These studies have been supported by the National Cancer Institute of Canada.

Received 6/27/68. Accepted 11/30/68.