Rat liver in vivo replicative DNA synthesis test for short-term prediction of nongenotoxic (Ames-negative) hepatocarcinogenicity: a collaborative study of the Nongenotoxic Carcinogen Study Group of Japan.
A collaborative study was conducted to evaluate whether a replicative DNA synthesis (RDS) test using the rat liver can detect nongenotoxic (Ames-negative) hepatocarcinogens with three or seven daily administrations at dose-levels effective in long-term bioassays. The assay methods were well-validated by the 14 participants. Of six compounds tested, carbon tetrachloride (50 and 100 mg/kg), clofibrate (125 and 250 mg/kg), diethylstilbestrol (0.125 and 0.25 mg/kg) and urethane (100 mg/kg) gave positive results, methyl carbamate (200 and 400 mg/kg) exerted equivocal effects, and D,L-ethionine (125 mg/kg) failed to elevate RDS. These findings suggest that the RDS test can detect many nongenotoxic rat hepatocarcinogens with short-term administration at dose-levels used in long-term bioassays.
Uno
Y
Y
Toxicology Laboratory, Yokohama Research Center, Mitsubishi Chemical Co., Japan. 1306005@cc.m-kagaku.co.jp
Matsuura
K
K
Miyagawa
M
M
Takasawa
H
H
Tanifuji
H
H
Abe
K
K
Akimoto
A
A
Asanoma
K
K
Baba
K
K
Daigo
H
H
Hagiwara
T
T
Hirano
K
K
Inoue
T
T
Kawano
Y
Y
Kijima
K
K
Sato
F
F
Shibata-Yoshida
K
K
Yamamura
E
E
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity; D001973:Bromodeoxyuridine / Q000633:toxicity; D015197:Carcinogenicity Tests / Q000379:methods*; D004247:DNA / Q000096:biosynthesis*; D004261:DNA Replication / Q000187:drug effects*; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009152:Mutagenicity Tests / Q000379:methods*; D051381:Rats; D011916:Rats, Inbred F344
D000964:Antimetabolites, Antineoplastic; D004247:DNA; D001973:Bromodeoxyuridine