Current and emerging challenges in toxicopathology: carcinogenic threshold of phenobarbital and proof of arsenic carcinogenicity using rat medium-term bioassays for carcinogens.
For the last 25 years, Prof. Nobuyuki Ito and his laboratory have focused on the development of liver medium-term bioassay system for detection of carcinogens in F344 rats utilizing glutathione S-transferase placental form (GST-P)-positive foci as an end point marker. In this presentation, the outline and samples of medium-term bioassay systems were described. Furthermore, our data demonstrated the presence of a threshold for the non-genotoxic carcinogen, phenobarbital (PB), and the lack of linearity in the low-dose area of the dose-response curve, providing evidence for hormesis. In addition, the establishment and applications of multiorgan carcinogenicity bioassay (DMBDD model), used for the examination of the carcinogenicity of genotoxic and non-genotoxic chemicals, are discussed. Dimethylarsinic acid, one of organic arsenics, was found to be carcinogenic in rat bladder using DMBDD model and carcinogenicity test.
Fukushima
Shoji
S
First Department of Pathology, Osaka City University Medical School, Abeno-ku, Asahi-machi 1-4-3, Osaka 545-8585, Japan. fukuchan@med.osaka-cu.ac.jp
Morimura
Keiichirou
K
Wanibuchi
Hideki
H
Kinoshita
Anna
A
Salim
Elsayed I
EI
D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D001681:Biological Assay; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D010336:Pathology; D010634:Phenobarbital / Q000633:toxicity*; D051381:Rats; D014116:Toxicology
D002273:Carcinogens; D001151:Arsenic; D010634:Phenobarbital