FREE AMINO ACIDS IN BLOOD. V 429 
All of the drugs that affect the hematopoietic system change the levels of sulfur 
amino acids. A marked drop in the taurine level is observed after myleran or dimethyl- 
myleran administration. A similar finding is reported after nitrogen mustard injection 
(see part IV). In contrast to the effect of nitrogen mustard, glutathione has been 
observed to remain near the control level or to increase in cells after dimethylmyleran, 
while nitrogen mustard produces a drop in the glutathione level. One of the major 
differences between the effects of nitrogen mustard and the myleran series of com- 
pounds is the effect on the glutamine levels of cells and plasma. Nitrogen mustard 
produces a definite drop in the glutamine levels, while myleran and dimethylmyleran 
either do not change the level or increase it. Nitrogen mustard and the cytotoxic 
myleran series of drugs have one thing in common: the drugs tend to produce a 
marked fall in the free amino acids of leukocytes. This decrease may be seen in 
plasma and erythrocytes in some cases. This loss of the free amino acid pool is related 
to cell damage and indicates gross changes in permeability and concentrative up- 
take after drug administration. 
The study of such labile constituents as free amino acids is complicated by the 
fact that a good deal of fluctuation of the levels occurs in plasma and cells in untreated 
patients and normal individuals. All or some of the free amino acids may first de- 
crease (or increase) and then increase (or decrease) after drug administration. The 
appreciation of the nature of these changes is important and it must be understood 
that the study of one blood sample from a patient before (or after) treatment will 
not give reliable results. The variable nature of results reported in the literature is 
undoubtedly related in part to the inadequacies of studies based on small numbers 
of samples. 
The results of several studies of the distribution and excretion of isotopically 
labeled myleran and related compounds and the 77 vitro reactions of these compounds 
have been published (refs. 34-39). These studies have demonstrated the interaction both 
in vityo and im vivo of myleran with cysteine and suggest that an important part of 
the mode of action of myleran may be related to reaction with sulfhydryl groups. The 
small amounts of drug necessary to produce an 7m vivo effect suggests to us that such 
reactions are most probably with protein sulfhydryl groups. The hypothesis that 
sulfhydryl compounds are involved in the action of myleran im vivo gains some 
support from our observations on free amino acids since the levels of sulfur-contain- 
ing amino compounds have been found to change after administration of the drug. 
Additional effects, probably at the enzyme level, are indicated by changes in the 
levels of other amino acids. 
References p. 447/448 
