Detection of teratogens in the Drosophila embryonic cell culture test: assay of 100 chemicals.

Abstract

An in vitro assay of teratogenesis has been developed that utilizes Drosophila embryonic cell cultures. The endpoint selected in assessing the teratogenic potential of any substance involves detection of interference with normal muscle and/or neuron differentiation. In the validation phase of this project, 100 chemicals were tested. With drugs for which extensive reliable mammalian data are available, the results in the Drosophila assay equate rather favorably with those observed in animals and humans (i.e., a low percentage of false positives and false negatives has been obtained). In an effort to determine if strain differences exist and also to establish that the system shows a dose response, cultures from three wild-type Drosophila strains (Canton S, Canton S109, and Oregon R) were tested. Dose-response differences were observed when diethylstilbestrol, diphenylhydantoin, imipramine, testosterone, and tolbutamide were added to the cultures. These results suggest that the Drosophila assay, with further testing and refinements, might be capable of identifying agents of high teratogenic potential by their effect on neurons and muscle differentiation. Furthermore, sensitive strains might be used to study mechanisms of abnormal development and gene involvement in teratogenic resistance.