To further characterize the Drosophila-based prescreen to detect developmental toxicants, the following 8 chemicals were evaluated - methyl mercury chloride (MMC), methotrexate (MTX), L-phenylalanine (LPA), sodium arsenate heptahydrate (SAH), cadmium chloride (CC), vinblastine sulfate (VBS), aminopterin (APN) and mitomycin C (MC). All of the test agents are mammalian developmental toxicants and/or teratogens. One-to-three experiments, each employing multiple concentrations and including a concurrent control, were conducted with each chemical using our published protocol (Teratogenesis, Carcinogenesis, and Mutagenesis 11:147-173, 1991). Drosophila were exposed throughout development (egg through third instar larva) in culture vials to medium containing the test chemical. A mated, untreated, Oregon-R wild-type female (Mid-American Drosophila Stock Center, BGSU, Ohio) was added to each vial and allowed to oviposit for 20 hours, then removed. Emerging offspring were collected over 10 days, and examined microscopically (25x) for bent humeral bristles and wing blade notches, morphological defects shown to occur with an increased incidence in flies exposed to developmental toxicants. In each experiment, the incidence of the two defects at each concentration was compared to the controls using chi-square. In cases where replicate data were available at a given concentration, incidence data were also pooled and compared to the pooled controls. The incidence of bent humeral bristles was statistically increased (p<0.05) in flies exposed to MMC, LPA, SAH, CC, VBS, and MC. VBS also statistically increased (p<0.05) the incidence of eye defects. The incidence of wing blade defects was statistically increased (p<0.05) in flies exposed to MTX and APN. These results with 8 diverse chemicals provide additional support for increased utilization of this assay as a prescreen for the detection of developmental toxicants.
The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah