Lack of Modifying Effect of Glycerol in Pulmonary Carcinogenesis in rasH2 Mice Induced by Urethane or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).

Abstract

Glycerol has been reported to have a promoting effect in pulmonary tumorigenesis induced by 4-nitroquinoline-1-oxide (4NQO) in ddY mice, but not in mice pretreated with urethane (UR) or 3-methylcholanthrene (3MC). To investigate the modifying effects of glycerol on the development of lung tumors induced by UR or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), transgenic CB6F1 mice carrying the human proto-type c-Ha-ras gene (rasH2 mice) and their wild littermates (non-Tg mice) were given a single intraperitoneal injection of UR or NNK. One week after the treatment of the carcinogen, they were allowed to drink 5% solution of glycerol ad libitum for 26 weeks. In rasH2 mice, alveolar/bronchiolar hyperplasias, adenomas, and carcinomas were induced in UR alone, UR + glycerol, NNK alone, and NNK + glycerol groups, but there were no significant differences in the incidences and multiplicity between UR alone and UR + glycerol groups or NNK alone and NNK + glycerol groups. In non-Tg mice, hyperplasias and adenomas were induced in UR alone, UR + glycerol, NNK alone, and NNK + glycerol groups, but no significant difference was observed between UR alone and UR + glycerol groups or NNK alone and NNK + glycerol groups. These results suggest that glycerol does not have a promoting effect in pulmonary carcinogenesis in rasH2 mice induced by urethane or NNK.