The in vivo-in vitro replicative DNA synthesis (RDS) test with hepatocytes prepared from male B6C3F1 mice as an early prediction assay for putative nongenotoxic (Ames-negative) mouse hepatocarcinogens

Miyagawa, M; Takasawa, H; Sugiyama, A; Inoue, Y; Murata, T; Uno, Y; Yoshikawa, K

HERO ID

661834

Reference Type

Journal Article

Year

1995

Language

English

PMID

7791810

HERO ID 661834
In Press No
Year 1995
Title The in vivo-in vitro replicative DNA synthesis (RDS) test with hepatocytes prepared from male B6C3F1 mice as an early prediction assay for putative nongenotoxic (Ames-negative) mouse hepatocarcinogens
Authors Miyagawa, M; Takasawa, H; Sugiyama, A; Inoue, Y; Murata, T; Uno, Y; Yoshikawa, K
Journal Mutation Research: Genetic Toxicology
Volume 343
Issue 2-3
Page Numbers 157-183
Abstract To assess the efficacy of the in vivo-in vitro hepatocyte replicative DNA synthesis (RDS) test as a short-term assay, 41 putative nongenotoxic (Ames-negative) mouse hepatocarcinogens, as well as 31 noncarcinogens, were examined using male 8-week-old B6C3F1 mice and an in vitro [methyl-3]thymidine-incorporation technique. Animals were exposed to the maximum tolerated dose (MTD) and 1/2 MTD of each chemical by gavage and after 24, 39 or 48 h, hepatocytes were prepared with a collagenase-perfusion technique. Assessment of the distribution of spontaneous RDS in a total of 337 control mice gave an average incidence of 0.15 +/- 0.08% within the range of 0 to 0.39% (mean +/- 3 x SE) with a 99.7% probability. Values of 0.4% or more for RDS incidences induced by test samples were therefore judged as indicating a positive response in our RDS test. Under the experimental conditions applied, 32 of 41 putative nongenotoxic hepatocarcinogens gave clear positive responses (positive sensitivity: 78%), and of 31 noncarcinogens 25 samples gave negative responses (negative specificity: 81%), thus giving an overall concordance for the RDS test with long-term findings of 79%.
Doi 10.1016/0165-1218(95)90082-9
Pmid 7791810
Wosid WOS:A1995RD71200009
Url http://www.sciencedirect.com/science/article/pii/0165121895900829
Is Certified Translation No
Dupe Override No
Comments Authoring Organization: HASKELL LAB
Is Public Yes
Language Text English
Keyword Replicative DNA synthesis; Cell proliferation; RDS test; Mouse liver; Nongenotoxic mouse hepatocarcinogens; Noncarcinogens
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