Dose-dependent promotion by phenylethyl isothiocyanate, a known chemopreventer, of two-stage rat urinary bladder and liver carcinogenesis.
The effects of phenylethyl isothiocyanate (PEITC) on urinary bladder and liver carcinogenesis were analyzed in a rat model. Diets containing 0.1%, 0.05%, or 0.01% PEITC were administered for 32 wk to male Fischer 344 rats with and without pretreatment with an injection of diethylnitrosamine (200 mg/kg body wt i.p.) and 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in the drinking water for 4 wk for initiation. In the initiated groups, PEITC administration significantly increased the incidences of papillary or nodular hyperplasia, dysplasia, and transitional cell carcinomas at higher doses of 0.01%, 0.01%, and 0.05%, respectively, compared with the control group, given initiation alone, in a dose-dependent manner. Without initiation, administration of 0.1% and 0.05% PEITC induced simple and papillary or nodular hyperplasia and dysplasia in the urinary bladder. In the liver, induction of glutathione S-transferase placental form-positive foci was dose dependently enhanced by PEITC administration, but the incidences of liver tumors were not different among the groups. From the present experiment, we can conclude that > 0.01% PEITC enhances rat urinary bladder carcinogenesis, while weakly promoting hepatocarcinogenesis. In addition, it is suggested that > 0.05% PEITC has tumorigenic potential.
Ogawa
K
K
First Department of Pathology, Nagoya City University Medical School, Nagoya 467-8601, Japan. kogawa@med.nagoya-cu.ac.jp
Hirose
M
M
Sugiura
S
S
Cui
L
L
Imaida
K
K
Ogiso
T
T
Shirai
T
T
D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D001835:Body Weight; D002273:Carcinogens / Q000008:administration & dosage; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D006965:Hyperplasia; D017879:Isothiocyanates / Q000008:administration & dosage*; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009929:Organ Size; D051381:Rats; D011916:Rats, Inbred F344; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000473:pathology
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D017879:Isothiocyanates; C058305:phenethyl isothiocyanate