4-Methylthio-3-butenyl isothiocyanate (raphasatin) exerts chemopreventive effects against esophageal carcinogenesis in rats.
To examine the effects of 4-methylthio-3-butenyl isothiocyanate on esophageal carcinogenesis, male 6-week-old F344 rats were subcutaneously injected with 0.5 mg/kg body weightN-nitrosomethylbenzylamine three times per week for 5 weeks and fed a diet supplemented with 80 ppm 4-methylthio-3-butenyl isothiocyanate, equivalent to 6.05 mg/kg body weight/day for the initiation stage, 4.03 mg/kg body weight/day for the promotion stage, or 4.79 mg/kg body weight/day for all stages. Although the incidence of lesions was not affected by 4-methylthio-3-butenyl isothiocyanate treatment, the multiplicity of squamous cell papilloma in the esophagus was significantly decreased in rats in the 4-methylthio-3-butenyl isothiocyanate initiation stage group (1.13 ± 0.74), 4-methylthio-3-butenyl isothiocyanate promotion stage group (1.47 ± 0.99), and 4-methylthio-3-butenyl isothiocyanate all stage group (1.47 ± 1.13) as compared with rats treated withN-nitrosomethylbenzylamine alone (3.00 ± 1.46). Immunohistochemical analysis revealed that 4-methylthio-3-butenyl isothiocyanate induced apoptosis, suppressed cell proliferation, and increased p21 expression when administered in the promotion phase. These modifying effects were not observed in the rats treated with 4-methylthio-3-butenyl isothiocyanate alone. Our results indicated that 4-methylthio-3-butenyl isothiocyanate may exert chemopreventive effects againstN-nitrosomethylbenzylamine-induced esophageal carcinogenesis in rats.
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan; Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu, Gifu501-1193, Japan.
Isamu
I
Suzuki
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Young-Man
YM
Cho
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan; Department of Pharmacology, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Tadashi
T
Hirata
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Takeshi
T
Toyoda
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Jun-Ichi
JI
Akagi
Faculty of Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Shimogamohangi-cho, Sakyo-ku, Kyoto 606-8522, Japan; Kyoto Prefectural Agriculture, Forestry & Fisheries Technology Center, 9 Wakunari, Amarube, Kameoka, Kyoto 621-0806, Japan.
Yasushi
Y
Nakamura
Faculty of Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Shimogamohangi-cho, Sakyo-ku, Kyoto 606-8522, Japan; Department of Food Science, Korea Christian University, Kkachisan-ro 24-gil, Gangseo-gu 47, Seoul 07661, Republic of Korea.
Eun Young
EY
Park
Faculty of Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Shimogamohangi-cho, Sakyo-ku, Kyoto 606-8522, Japan.
Azusa
A
Sasaki
Faculty of Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Shimogamohangi-cho, Sakyo-ku, Kyoto 606-8522, Japan.
Takako
T
Nakamura
Department of Food Science and Biotechnology, Kagoshima University, 1-21-24 Korimoto, Kagoshima, Kagoshima 890-0065, Japan.
Shigehisa
S
Okamoto
Kyoto Prefectural Agriculture, Forestry & Fisheries Technology Center, 9 Wakunari, Amarube, Kameoka, Kyoto 621-0806, Japan.
Koji
K
Shirota
Kyoto Prefectural Agriculture, Forestry & Fisheries Technology Center, 9 Wakunari, Amarube, Kameoka, Kyoto 621-0806, Japan.
Noboru
N
Suetome
Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu, Gifu501-1193, Japan; Biological Safety Research Center, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Akiyoshi
A
Nishikawa
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Kumiko
K
Ogawa
4-methylthio-3-butenyl isothiocyanate; N-nitrosomethylbenzylamine; chemoprevention; esophageal cancer; raphasatin