title: Toxic effects of 4-methylthio-3-butenyl isothiocyanate (Raphasatin) in the rat urinary bladder without genotoxicity.
abstract: 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-1body 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.
authors.affiliation: Division of Pathology, National Institute of Health Sciences, Tokyo, 158-8501, Japan.|Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, Gifu, 501-1193, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Suzuki
authors.affiliation: Division of Pathology, National Institute of Health Sciences, Tokyo, 158-8501, Japan.
authors.forename: Young-Man
authors.initials: YM
authors.lastname: Cho
authors.affiliation: Division of Pathology, National Institute of Health Sciences, Tokyo, 158-8501, Japan.|Department of Pharmacology, School of Pharmacy, Showa University, Tokyo, 142-8555, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hirata
authors.affiliation: Division of Pathology, National Institute of Health Sciences, Tokyo, 158-8501, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Toyoda
authors.affiliation: Division of Pathology, National Institute of Health Sciences, Tokyo, 158-8501, Japan.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Akagi
authors.affiliation: Faculty of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, 606-8522, Japan.|Kyoto Prefectural Agriculture, Forestry & Fisheries Technology Center, Kyoto, 621-0806, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Faculty of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, 606-8522, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Sasaki
authors.affiliation: Faculty of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, 606-8522, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Food Science and Biotechnology, Kagoshima University, Kagoshima, Kagoshima, 890-0065, Japan.
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Okamoto
authors.affiliation: Kyoto Prefectural Agriculture, Forestry & Fisheries Technology Center, Kyoto, 621-0806, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Shirota
authors.affiliation: Kyoto Prefectural Agriculture, Forestry & Fisheries Technology Center, Kyoto, 621-0806, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Suetome
authors.affiliation: Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, Gifu, 501-1193, Japan.|Biological Safety Research Center, National Institute of Health Sciences, Tokyo, 158-8501, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishikawa
authors.affiliation: Division of Pathology, National Institute of Health Sciences, Tokyo, 158-8501, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000187:drug effects; D004249:DNA Damage; D004435:Eating / Q000187:drug effects; D017879:Isothiocyanates / Q000633:toxicity*; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology; D001745:Urinary Bladder Diseases / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology
chemical_list: C447639:4-(methylthio)-3-butenyl isothiocyanate; D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D009153:Mutagens
keywords: 4-methylthio-3-butenyl isothiocyanate; Raphasatin; genotoxicity; phenethyl isothiocyanate; urinary bladder toxicity