title: 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.
abstract: 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.
authors.affiliation: Toxicology Laboratory, Yokohama Research Center, Mitsubishi Chemical Co., Japan. 1306005@cc.m-kagaku.co.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Uno
authors.forename: K
authors.initials: K
authors.lastname: Matsuura
authors.forename: M
authors.initials: M
authors.lastname: Miyagawa
authors.forename: H
authors.initials: H
authors.lastname: Takasawa
authors.forename: H
authors.initials: H
authors.lastname: Tanifuji
authors.forename: K
authors.initials: K
authors.lastname: Abe
authors.forename: A
authors.initials: A
authors.lastname: Akimoto
authors.forename: K
authors.initials: K
authors.lastname: Asanoma
authors.forename: K
authors.initials: K
authors.lastname: Baba
authors.forename: H
authors.initials: H
authors.lastname: Daigo
authors.forename: T
authors.initials: T
authors.lastname: Hagiwara
authors.forename: K
authors.initials: K
authors.lastname: Hirano
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.forename: Y
authors.initials: Y
authors.lastname: Kawano
authors.forename: K
authors.initials: K
authors.lastname: Kijima
authors.forename: F
authors.initials: F
authors.lastname: Sato
authors.forename: K
authors.initials: K
authors.lastname: Shibata-Yoshida
authors.forename: E
authors.initials: E
authors.lastname: Yamamura
mesh_terms: 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
chemical_list: D000964:Antimetabolites, Antineoplastic; D004247:DNA; D001973:Bromodeoxyuridine