A medium-term, rapid rat bioassay model for the detection of carcinogenic potential of chemicals.
The Ito Liver Model and the Ito Multi-organ Model are used in conjunction and constitute an efficient and rapid bioassay for the identification of both genotoxic and nongenotoxic carcinogenic chemicals. The Ito Liver Model is an 8-week bioassay system that uses the number and size of foci of hepatocytes positive for glutathione S-transferase placental form (GST-P) as the end-point marker. One hundred fifty-nine compounds were tested using the Ito Liver Model: 61 of 66 hepatocarcinogens tested positive, and 10 of 43 nonliver carcinogens were also positive. The false-positive detection of noncarcinogens was low; a single false-positive result was obtained from the 50 noncarcinogens tested. Since more than half of all known carcinogens are hepatocarcinogens in rodents, the initial 8-week bioassay is able to detect most carcinogens. The Ito Multi-organ Model is a 28-week bioassay system for the detection of carcinogens that were not identified by the Ito Liver Model. Results are evaluated by preneoplastic and neoplastic lesions in major organs. Forty-four compounds were tested using the Ito Multi-organ Model: 17 out of 17 liver carcinogens were positive, and 19 out of 22 (86%) nonliver carcinogens were positive. None of the five noncarcinogens tested positive.
Tsuda
Hiroyuki
H
Nanotoxicology Project, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-ku, Mizuho-cho, Nagoya 467-8601, Japan. htsuda@med.nagoya-cu ac.jp
Futakuchi
Mitsuru
M
Fukamachi
Katsumi
K
Shirai
Tomoyuki
T
Imaida
Katsumi
K
Fukushima
Shoji
S
Tatematsu
Masae
M
Furukawa
Fumio
F
Tamano
Seiko
S
Ito
Nobuyuki
N
D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods*; D004195:Disease Models, Animal; D051549:Glutathione S-Transferase pi / Q000032:analysis; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D051549:Glutathione S-Transferase pi; C496558:Gstp1 protein, rat