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Carcinogenicity of 1-(4-amino-2-methylpyrimidine-5-yl)-methyl-3-(2-chloroethyl)-3- nitrosoureahydrochloride and three related N-nitroso derivatives following repeated intravenous administration to male Wistar rats.

Abstract
Long-term toxic evaluation of 1-(4-amino-2-methylpyrimidine-5-yl)-methyl-3- (2-chloroethyl)-3-nitrosoureahydrochloride (ACNU), 1-(2-chloroethyl)-1-nitroso-3-(methylene-2-pyridylium)-urea- hydrochloride (CNMPU), 1-(2-chloroethyl)-1-nitroso-3-(4-thiomorpholino)-urea (CNTMU) and 4-[N-(2-chloroethyl)-N-nitrosocarbamoyl]-morpholine (CNCM) which were administered each at five dosages, adapted to the clinical situation, revealed significantly increased tumor risks for the first three agents in the lung and the adrenal gland. Additionally, CNTMU and ACNU induced a significant rise in the tumor load of the neurogenic tissue; the latter compound, being in clinical use, was associated with a significantly increased number of mammary tumors as well. CNCM, however, did not exhibit significantly elevated carcinogenic activity, although the overall tumor load was up to 2.4-fold increased compared to controls. The results indicate no advantage of the newly developed ACNU with respect to its inherent carcinogenic risk as compared to clinically established 2-chloroethyl-N-nitroso derivatives.
AuthorsM R Berger, E Petru, D Schmähl
JournalOncology (Oncology) Vol. 45 Issue 2 Pg. 127-33 ( 1988) ISSN: 0030-2414 [Print] Switzerland
PMID3162572 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents
  • Nitrogen Mustard Compounds
  • Nitroso Compounds
  • Nitrosourea Compounds
  • Nimustine
  • 1-(2-chloroethyl)-1-nitroso-3-(4-thiomorpholino)urea
  • 1-(2-chloroethyl)-1-nitroso-3-(methylene-2-pyridinyl)urea
  • 4-(N-(2-chloroethyl)-N-nitrosocarbamoyl)morpholine
Topics
  • Animals
  • Antineoplastic Agents (toxicity)
  • Body Weight (drug effects)
  • Injections, Intravenous
  • Male
  • Neoplasms, Experimental (chemically induced)
  • Nimustine
  • Nitrogen Mustard Compounds (toxicity)
  • Nitroso Compounds (toxicity)
  • Nitrosourea Compounds (toxicity)
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship

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