Open AccessEnhancement of urinary bladder carcinogenesis by combined treatment with benzyl isothiocyanate and N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine in rats after initiation
Author(s) -
Okazaki Kazushi,
Umemura Takashi,
Imazawa Takayoshi,
Nishikawa Akiyoshi,
Masegi Toshiaki,
Hirose Masao
Publication year - 2003
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2003.tb01383.x
Subject(s) - benzyl isothiocyanate , nitrosamine , carcinogen , carcinogenesis , hyperplasia , urinary system , urinary bladder , medicine , basal (medicine) , isothiocyanate , endocrinology , chemistry , cancer , biochemistry , insulin
Previously we reported that benzyl isothiocyanate (BITC) strongly enhanced rat urinary bladder carcinogenesis after initiation with N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine (BBN), while potently inhibiting BBN‐induction of lesions when given simultaneously with the carcinogen. In the present experiment, the effects of simultaneous treatment with BITC and low‐dose BBN on the postinitiation period of rat urinary bladder carcinogenesis were examined. After treatment with 500 ppm BBN for 4 weeks for initiation, groups of 20, 6‐week‐old, F344 male rats were given 25 ppm BBN alone, basal diet alone, or 100 or 1000 ppm BITC in the diet together with or without 25 ppm BBN in their drinking water for 36 weeks and then killed for autopsy. Further groups consisting of 10 rats each were similarly given BITC or the basal diet together with or without 25 ppm BBN, without initiation treatment. In the initiated groups receiving subsequent BBN exposure, papillary and nodular hyperplasia, dysplasia and carcinoma incidences were significantly increased, and they were further increased by the combined treatment with 100 and 1000 ppm BITC in a dosedependent manner. In the non‐initiation groups, carcinomas were only observed in a single rat in each of the BBN‐treated control and BBN/BITC 100 ppm treatment groups. The results indicate that simultaneous treatment with BITC and a low dose of BBN does not inhibit, but rather enhances rat urinary bladder carcinogenesis after appropriate initiation, and further suggest that BITC may be a human risk factor, at least in high‐risk populations.