Horseradish extract promotes urinary bladder carcinogenesis when administered to F344 rats in drinking water.
Horseradish extract (HRE), consisting mainly of a mixture of allyl isothiocyanate and other isothiocyanates, has been used as a food additive. To evaluate the potential hazards of HRE, a 104-week chronic study, a 2-week analysis of cell proliferation in the urinary bladder and a medium-term promotion bioassay of HRE were conducted with administration at concentrations of up to 0.04% HRE in the drinking water to male F344 rats. In the 104-week chronic study with 32 male rats per group, no treatment-related increases in the incidences of neoplastic lesions in any organ, including urinary bladder, were observed, except for simple hyperplasia in the urinary bladder in rats treated with HRE at concentrations of more than 0.01% (5.0 mg kg-1body weight day-1). In the promotion study, HRE treatment after N-butyl-N-(4-hydroxybutyl)nitrosamine initiation caused a clear increase in papillary or nodular hyperplasia, papilloma, and urothelial carcinoma of the urinary bladder in the groups given HRE for 13 weeks at doses higher than 0.005%, 0.01%, and 0.04% (2.7, 5.4 and 20.5 mg kg-1body weight day-1), respectively. In the 2-week cell proliferation analysis, treatment with HRE at concentrations greater than 0.005% (3.9 mg kg-1body weight day-1) caused transient increases in 5-bromo-2'-deoxyuridine labeling indices in the urothelium. Although clear tumor induction was not observed, administration of relatively low-dose HRE increased cell proliferation in the urothelium and exerted obvious promoting effects on rat urinary bladder carcinogenesis. Further studies are needed to elucidate the mode of action of HRE in the rat urinary bladder to facilitate data extrapolation from the present study and provide insights into risk assessment. Copyright © 2017 John Wiley & Sons, Ltd.
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.
Mai
M
Hasumura
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-Ku, Tokyo, 158-8501, Japan.|Central Animal Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Toshio
T
Imai
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-Ku, Tokyo, 158-8501, Japan.
Shigeaki
S
Takami
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
D000818:Animals; D031215:Armoracia / Q000737:chemistry / Q000633:toxicity*; D063646:Carcinogenesis / Q000139:chemically induced*; D002273:Carcinogens / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects*; D060766:Drinking Water; D017879:Isothiocyanates / Q000633:toxicity*; D010936:Plant Extracts / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D001749:Urinary Bladder Neoplasms / Q000209:etiology*
D002273:Carcinogens; D060766:Drinking Water; D017879:Isothiocyanates; D010936:Plant Extracts
horseradish extract; isothiocyanate; medium-term promotion bioassay; rats; tumorigenicity; urinary bladder