The diverse modification of N-butyl-N-(4-hydroxybutyl) nitrosamine induced carcinogenesis in urinary bladder by dibromodulcitol and dianhydrodulcitol.

Abstract

The effects of intravesical therapy with adriamycin, 1.6-dibromo-1.6-dideoxydulcitol (DBD) or with 1.6-dianhydrodulcitol (DAD) on bladder carcinogenesis were investigated in rats. To induce premalignant lesions in the urinary bladder female Sprague-Dawley rats received 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in their drinking water for 4 weeks and then post-treated intravesically with one of the antitumor drugs and examined once a week for 3 months. These antitumor drugs in healthy rats (i.e. without the pre-administration of BBN) did not cause any significant morphological changes in the urinary bladder after intravesical application once a week for 3 months. In the applied dose BBN alone induced only premalignant lesions in the urinary bladder. However, neoplastic lesions occurred in the groups treated with BBN and adriamycin (9 papillomas and 3 carcinomas in 14 animals). Similarly intravesical application of DBD after BBN administration resulted 5 carcinomas among the 11 animals. On the contrary no urinary bladder tumor was found in the animals treated with BBN and DAD. As DAD is one of the conversion products of DBD it is conceivable that the difference between DBD and DAD action may be due to the formation of other solvolytic product from DBD than DAD.