An in vivo-in vitro replicative DNA synthesis (RDS) test using rat hepatocytes as an early prediction assay for nongenotoxic hepatocarcinogens screening of 22 known positives and 25 noncarcinogens.
To evaluate the applicability of an in vivo-in vitro replicative DNA synthesis (RDS) test using rat hepatocytes, we conducted the RDS test with 22 nongenotoxic (Ames-negative) hepatocarcinogens and 25 noncarcinogens under our standardized conditions and judgement criteria. Compared to controls (RDS incidence of under 1.0%), the RDS test gave positive results for 18 hepatocarcinogens (positive sensitivity: 82%), and negative results for 20 noncarcinogens (negative specificity: 80%), and thus the overall concordance was 81%. These findings strongly suggest that the RDS test is an extremely useful method for early detection of nongenotoxic hepatocarcinogens.
Uno
Y
Y
Toxicology Laboratory, Mitsubishi Kasei Co., Yokohama, Japan.
Takasawa
H
H
Miyagawa
M
M
Inoue
Y
Y
Murata
T
T
Yoshikawa
K
K
D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D005069:Evaluation Studies as Topic; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012680:Sensitivity and Specificity
D002273:Carcinogens