Carcinogenicity of N-Nitrosomethyl(2-oxopropyl)amine in Syrian Hamsters

Parviz Pour, Ralph Gingell, Robert Langenbach, Donald Nagel, Carter Grandjean, Terence Lawson, Shahrokh Salmasi

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Abstract

7-Methylguanine was found in hydrolysates of liver and pancreas DNA from Syrian golden hamsters given a single dose of N-[1-14C]nitrosobis(2-oxopropyl)amine (BOP). This led us to examine the carcinogenicity of a potential methylating metabolite of BOP, N-nitrosomethyl(2-oxopropyl)amine (MOP). MOP was found to be a potent pancreatic carcinogen by either single or weekly s.c. injections. A single MOP treatment (25 mg/kg body weight) induced ductular adenomas and/or adenocarcinomas in 80% of the hamsters. A higher incidence of these neoplasms was found in 93% and 87% of animals receiving, respectively, 3.5 and 1.75 mg MOP per kg body weight weekly for life. However, the lower dose (0.87 mg/kg body weight) was less effective, resulting in a 33% tumor incidence. Compared with the known potent pancreatic carcinogen BOP, MOP seemed to have a greater affinity for the pancreas since considerably lower doses were required to induce similar incidences of equivalent pancreatic tumors. Like BOP, MOP caused tumors of the liver (7 to 100% incidence), kidneys (7 to 80% incidence), and vascular system (7 to 27% incidence). However, in contrast to BOP, which was noncarcinogenic to the upper respiratory tract, MOP-treated animals developed a high incidence of nasal cavity tumors (40% after a single treatment and 27 to 100% after weekly injections). The mutagenesis studies using hamster liver cell-mediated V79 cells confirmed the stronger effect of MOP compared to BOP. The assumption that MOP might be a proximate carcinogenic metabolite of BOP could not be substantiated by our methods for determining the in vivo and in vitro metabolites of BOP.

Original languageEnglish (US)
Pages (from-to)3585-3590
Number of pages6
JournalCancer Research
Volume40
Issue number10
Publication statusPublished - Oct 1 1980

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Pour, P., Gingell, R., Langenbach, R., Nagel, D., Grandjean, C., Lawson, T., & Salmasi, S. (1980). Carcinogenicity of N-Nitrosomethyl(2-oxopropyl)amine in Syrian Hamsters. Cancer Research, 40(10), 3585-3590.