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.
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
Shoji
S
Fukushima
Keiichirou
K
Morimura
Hideki
H
Wanibuchi
Anna
A
Kinoshita
Elsayed I
EI
Salim
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