Caenorhabditis elegans as a model in developmental toxicology

Abstract

A number of practical advantages have made the nematode Caenorhabditis elegans a useful model for genetic and developmental biological research. These same advantages, along with conservation of disease and stress response pathways, availability of mutant and transgenic strains, and wealth of biological information, have led to the increased use of C. elegans in toxicological studies. Although the potential to study the mechanisms of developmental toxicology in C. elegans is promising, embryonic and larval growth tests to identify compounds that affect the nematode have remained the primary use of C. elegans in developmental toxicology. Here, we describe a C. elegans larval growth and development assay for medium- and high-throughput screening using the COPAS Biosort flow cytometer and provide descriptions of the data and subsequent analysis.

Figure 1. Adult C. elegans hermaphrodite

Image was acquired at 20× magnification.

Figure 2. C. elegans growth from L1 to adult

Untreated L1 nematodes were incubated at 20°C and sampled at 0 h (black), 24 h (red), 48 h (green), and 72 h (blue). Upper panel, scatter-plot of optical density (log(EXT)) versus length (log(TOF)). Each point corresponds to an individual nematode. Lower panel, frequency distributions of log(EXT) versus numbers of nematodes. At 72 h, adult nematodes (high EXT, TOF) and their offspring (low EXT, TOF) were observed.

Figure 3. Observed and predicted frequency distributions of log(EXT) measurements after 48-h exposure to cadmium chloride

The loading distribution (green line) and the observed measurements (red line) after 48-h for untreated and groups exposed to eleven concentrations of cadmium chloride are presented. The estimated lognormal distribution describing the extraneous noise measurements for each cohort (black line) and the predicted frequency distribution for the nematode measurements based on the growth model (blue line) are also presented.