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Toxic effects of 4‐methylthio‐3‐butenyl isothiocyanate ( Raphasatin ) in the rat urinary bladder without genotoxicity
Author(s) -
Suzuki Isamu,
Cho YoungMan,
Hirata Tadashi,
Toyoda Takeshi,
Akagi Junichi,
Nakamura Yasushi,
Sasaki Azusa,
Nakamura Takako,
Okamoto Shigehisa,
Shirota Koji,
Suetome Noboru,
Nishikawa Akiyoshi,
Ogawa Kumiko
Publication year - 2017
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.3384
Subject(s) - genotoxicity , phenethyl isothiocyanate , urinary system , toxicity , urinary bladder , carcinogen , nitrosamine , micronucleus test , pharmacology , chemistry , micronucleus , in vivo , isothiocyanate , toxicology , medicine , biology , biochemistry , microbiology and biotechnology
We recently reported that 4‐methylthio‐3‐butenyl isothiocyanate (MTBITC) exerts chemopreventive effects on the rat esophageal carcinogenesis model at a low dose of 80 ppm in a diet. In contrast, some isothiocyanates (ITCs) have been reported to cause toxic effects, promotion activity, and/or carcinogenic potential in the urinary bladder of rats. In the present study, we investigated whether MTBITC had toxic effects in the urinary bladder similar to other ITCs, such as phenethyl ITC (PEITC). First, to examine the early toxicity of MTBITC, rats were fed a diet supplemented with 100, 300 or 1000 ppm MTBITC for 14 days. Treatment with 1000 ppm MTBITC caused increased organ weights and histopathological changes in the urinary bladder, producing lesions similar to those of 1000 ppm PEITC. In contrast, rats treated with 100 or 300 ppm MTBITC showed no signs of toxicity. Additionally, we performed in vivo genotoxicity studies to clarify whether MTBITC may exhibit a carcinogenic potential through a genotoxic mechanism in rats. Rats were treated with MTBITC for 3 days at doses of 10, 30 or 90 mg kg −1 body weight by gavage, and comet assays in the urinary bladder and micronucleus assays in the bone marrow were performed. No genotoxic changes were observed after treatment with MTBITC at all doses. Overall, these results suggested that the effects of MTBITC in the rat urinary bladder are less than those of PEITC, but that MTBITC could have toxic effects through a nongenotoxic mechanism in the urinary bladder of rats at high doses. Copyright © 2016 John Wiley & Sons, Ltd.