Abstract
The incidence of spontaeous mammary tumors in female rodents was increased in 2-year oncogenic studies of (-)-(R)-5-[2-[[2-(o-ethoxyphenoxy)ethyl] amino] propyl-2-methoxybenzenesulfon-amide hydrochloride (tamsulosin hydroch-loride) administered with diet. This study was carried out to clarify mammary carcinogenic potential of tamsulosin hydrochlor-ide, in particular whether these mammary tumors are prolactin dependent or not, by a two-stage carcinogenesis study. Sprague-Dawley rats were initially given a single oral dose (20mg/rat) of 7, 12-dimethylbenzanthracene (DMBA). Two weeks later, they were divided into 4 groups as follows: 1) DMBA control, 2) 0.1% tamsulosin hydrochloride in diet, 3) 0.1% tamsulosin hydrochloride in diet and daily s.c. injections of 1mg/rat 2-bromo-alpha-ergocryptine mesylate (CB-154), a potent suppressor of pituitary prolactin secretion, and 4) daily s. c. injections of 1mg/rat CB-154. The non-treated control group was also prepared. Administration periods of the compounds were 15 weeks in females and 39 weeks in males. At the end of the treatment period, all surviving rats were necropsied, and then all mammary nodular lesions were fixed in phosphate buffered 10% formalin, and were weighed after fixation. Histopathological examination revealed that tamsulosin hydrochloride at 0.1% dietary dose caused a slight promoting effect on mammary tumorigenesis, whereas the combination of CB-154 with tamsulosin hydrochloride inhibited this effect. The results strongly suggest that mammary tumors induced by tamsulosin hydrochloride administration were not due to direct effect of this compound but were possibly secondary effect through the pharmacological effect increasing the serum prolactin level of this drug.
