Inhibitory effects of 2-mercaptoethane sulfonate and 6-phenylhexyl isothiocyanate on urinary bladder tumorigenesis in rats induced by N-butyl-N-(4-hydroxybutyl)nitrosamine.
The effects of 2-mercaptoethane sulfonate (MESNA) and phenethyl and 6-phenylhexyl isothiocyanates (PEITC and PHITC) on urinary bladder tumorigenesis were investigated in Wistar rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN). A total of 190 male rats were divided into eight groups. Animals in groups 1, 3 and 4 were administered BHBN in drinking water (0.025%) and group 2 rats were given 0.025% BHBN plus 0.05% MESNA solution for 15 weeks. Rats in groups 3 and 4 were fed a diet supplemented with PEITC or PHITC at a dose level of 0.5 micromol/g for 16 weeks starting 1 week prior to the BHBN treatment. Rats in groups 5-7 served as MESNA, PEITC or PHITC alone controls. Group 8 served as a non-treatment control. The chromatographic profile of drinking water for group 2 animals indicated no chemical interaction between BHBN and MESNA. The incidences of papillomas in the bladder and total bladder tumors including transitional cell carcinomas were significantly (P<0.01) reduced in group 2 as compared to that in group 1. The multiplicities of papillomas or total bladder tumors were significantly (P<0.01) lower in group 2 and 4 rats treated with MESNA and PHITC, respectively, than in group 1 rats. The PEITC treatment, however, did not affect the BHBN-induced bladder tumorigenesis. No bladder tumors were found in animals of groups 5-8. The results in the present study clearly indicate that both MESNA and PHITC are potent chemopreventive agents against bladder tumor development in rats induced by BHBN.
Nishikawa
Akiyoshi
A
Division of Carcinogenesis and Molecular Epidemiology, American Health Foundation, 1 Dana Road, Valhalla, NY 10595, USA. nishikaw@nihs.go.jp
Morse
Mark A
MA
Chung
Fung Lung
FL
D000818:Animals; D002085:Butylhydroxybutylnitrosamine; D002273:Carcinogens; D017879:Isothiocyanates / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D015080:Mesna / Q000494:pharmacology*; D008956:Models, Chemical; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology
D002273:Carcinogens; D017879:Isothiocyanates; D020011:Protective Agents; C073279:6-phenylhexyl isothiocyanate; D002085:Butylhydroxybutylnitrosamine; D015080:Mesna