Carcinogenicity of 1-Methyl-1-nitrosourea in Nonhuman Primates

Abstract

The carcinogenic potential of 1-methyl-1-nitrosourea (MNU) was evaluated in three species (Macaca mulatta, M. fascicularis, and Cercopithecus aethiops) of nonhuman primates. A total of 43 monkeys received MNU for periods up to 96 months. Of the 13 monkeys necropsied thus far, 5 (38%) have had squamous cell carcinoma (SCA) of the oropharynx and/or esophagus, and 12 of the 13 (92%) have had some type of upper digestive tract lesion such as atrophy or dyskeratosis of the esophageal mucosa and esophagitis. All the animals receiving total doses of MNU exceeding 50 g developed SCA after approximately 5 years of exposure. Many parallels were noted between the esophageal SCA observed in the present series of monkeys and human esophageal carcinoma, including the clinical manifestations of the tumor and its complications, radiographic appearance, and morphology. Therefore, the MNU-induced lesions of the oropharynx and esophagus of primates may be a valuable model for the study of human esophageal carcinoma.