Retarding Effect of Glyceraldehyde on Benzpyrene Sarcoma Formation in Mice*

In an earlier experiment Riley and Wallace (8) showed that 0.5 cc. M/IO propionaldehyde injected subcutaneously into mice twice weekly for the 16 weeks during which tumors from a previous injection of 0.5 mgm. benzpyrene were to be expected, reduced the tumor yield from 36 to 22 per cent. In tissue culture it has been demonstrated that the growth and cellular activity of chick periosteal fibroblasts and of the cells of a dibenzanthracene chicken sarcoma are both inhibited at similar concentrations by a large series of aldehydes (11). Before such a generalization for aldehyde inhibition in vivo can be accepted, it is necessary to test the effect on tumor emergence of glyceraldehyde, which differs from other aldehydes in three ways. First, glyceraldehyde is itself a normal intermediate of phosphorylating carbohydrate breakdown. Second, glyceraldehyde in crystals and fresh solution exists in dimeric (dimolecular) form and hence closely resembles glucose. Like glucose, dimeric glyceraldehyde has a similar action in inhibiting the initial step of phosphorylating glycolysis (1). Third, after being in solution for over 3 days glyceraldehyde is entirely converted into its monomeric (monomolecular) form, and as such is believed to be a specific inhibitor of direct sugar breakdown without phosphorylation. This last effect, the inhibition of glycolysis, is brought about by only one optical component,/-glyceraldehyde, of the racemic mixture (2, 5). The inhibition by glyceraldehyde of anaerobic and aerobic glycolysis in tumor tissue was first pointed out by Mendel (4), and subsequently reported for chick embryo by Needham and his associates (6, 7). The question whether a special form of carbohydrate breakdown other than phosphorylating glycolysis is actually involved in the inhibition of glycolysis by glyceraldehyde has been raised by Macfarlane (3), although she was unable to offer a complete explanation of the specific inhibition of the/-isomeride. Siillmann (9, 10) has suggested that the inhibitory action of glyceraldehyde on carbohydrate breakdown may be