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The Effects of Alkylating Agents on the Incorporation of Glycine-1-C¹⁴ into Tissue Proteins in Vitro

( McGill-Montreal General Hospital Research Institute, 3619 University Street, Montreal, Canada)

The effects of a number of alkylating agents on the in vitro incorporation of glycine-1-C¹⁴ into the ethanol/acetone-insoluble fraction of Ehrlich ascites carcinoma cells have been studied. With the exception of 1:6-dimethanesulfonyl-D-mannitol, all inhibit (at the concentrations tested) this incorporation in varying degrees, with little or no effect on the respiration of the cells. The process of incorporation of glycine-1-C¹⁴ into tissue proteins is inhibited by alkylating agents in tumors, embryo, and normal adult tissues.

The inhibitory effect of an alkylating agent on the incorporation of glycine-1-C¹⁴ into the proteins of tissues increases with time of exposure of the cells to the agent. Different tissues have different susceptibilities to an alkylating agent, so far as inhibition of glycine-1-C¹⁴ incorporation is concerned.

Glucose is able to effect some reversal of the inhibitory effects of the alkylating agents studied in Ehrlich carcinoma cells, but none in liver.

Studies of the effects of di-(2-chloroethyl)amino hydrochloride show that, if inhibition of the process of glycine incorporation in Ehrlich ascites proteins is proportional to the amount of alkylating agent adsorbed on a cell receptor, the adsorption follows the Langmuir adsorption isotherm.

Received 6/ 2/60.