A model combining the whole embryo culture with human liver S-9 fraction for human teratogenic prediction.
The whole embryo culture system has proved particularly useful in evaluating the role of biotransformation in dysmorphogenic processes. Using the traditional method, information on the teratogenic potential of chemicals can be obtained, but the results are difficult to extrapolate to humans. In this study, a human liver S-9 fraction was used as an enzyme source for the bioactivation of cyclophosphamide (CP) in vitro, to assess whether this model mimics more nearly the human situation. CP is a well known rodent teratogen but probably is not teratogenic in humans. The effects were compared of Aroclor-1254-induced rat liver S-9, non-induced rat liver S-9 and human liver S-9 fractions on CP teratogenicity in vitro. CP (30 mug/ml) with non-induced rat S-9 (50 mul) did not cause a significant increase in adverse effects (46.7%), whereas 100% dysmorphogenic effects were shown with induced rat S-9 (30 mul, 50 mul). CP (30-150 mug/ml) did not produce dysmorphogenesis (below 35.5%) in the presence of human S-9 (50 mul).
Zhao
J
J
Drug Safety Assessment, Sandoz Ltd, CH-4002 Basel, Switzerland.
Krafft
N
N
Terlouw
G D
GD
Bechter
R
R