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Enzymatic Inactivation of N-Nitroso Compounds in Murine Blood Plasma¹

Pharmacology Laboratory, The Johns Hopkins Oncology Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205 [R. B. B.], and Department of Biology, The Johns Hopkins University, Baltimore, Maryland 21218 [S. L. A.]

Murine blood plasma rapidly inactivates nitrosamides and nitrosocarbamates but not nitrosoureas. The mechanism of this inactivation in murine blood plasma has been investigated. The vast majority of activity (>97%) was inhibited by serine hydroxylase inhibitors. Also, 92% of the activity was inhibited by bis(p-nitrophenyl)phosphate, a selective inhibitor of carboxylesterases. Decomposition products formed after blood plasma action on N-ethyl-N-nitrosoacetamide or N-methyl-N-nitrosoethylcarbamate were separated and identified by gas chromatography. The products formed were consistent with a hydrolytic cleavage of the amidic bond. These observations are consistent with the idea that the major active factor(s) in plasma is a carboxylesterase(s).

¹ This is Contribution 1266 from the Department of Biology, The Johns Hopkins University.

² Recipient of Grant 5-R01-CA16783 from the National Cancer Institute. To whom requests for reprints should be addressed.

³ Recipient of NIH National Research Service Award GM07231 while at the Johns Hopkins University. Present address: The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Department of Cell Biology (HMB 173), 6723 Bertner, Houston, TX 77030.

Received 5/29/84. Accepted 12/ 4/84.