The metabolic effects of urethan and N-methylformamide (NMF) on Escherichia coli were studied primarily by means of a chromatographic-autoradiographic technic which showed the effects of the inhibitors upon the formation of soluble intracellular metabolites derived from aspartate-14C.

NMF (16.5 mg/ml) caused a marked decrease in pyrimidine biosynthesis. The magnitude of this decrease with respect to growth inhibition approximated that exhibited by 6-azauracil, and the decrease was thus some indication that pyrimidine deficiency was a major cause of the observed inhibition of growth. However, we could find no evidence for inhibition of aspartate transcarbamylase, dihydroorotase, dihydroorotate dehydrogenase, or orotidylate decarboxylase by NMF.

Urethan (18.0 mg/ml) caused only a moderate decrease in pyrimidine biosynthesis, for which reason this effect was probably not the primary cause of growth inhibition. However, the extent to which pyrimidine biosynthesis was inhibited might be explained by the strongly inhibitory effect of urethan on aspartate transcarbamylase.

Urethan and NMF both caused increases in the pools of ribonucleoside triphosphates, probably by inhibiting phosphatase activities.

1

Supported by Cancer Chemotherapy National Service Center, National Cancer Institute, under NIH Contract No. PH43-66-29, and by grants from the American Cancer Society, the Alfred P. Sloan Foundation, and the Charles F. Kettering Foundation. This is the second paper in the series, Chromatographic Studies of Pyrimidine Metabolism. A preliminary report was presented at the Annual Meeting of the American Association for Cancer Research, Chicago, Illinois, April 1967.

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©1969 American Association for Cancer Research.
1969
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