The Caenorhabditis elegans worm Development and Activity Test (wDAT) can be used to differentiate between reversible and irreversible developmental effects

Abstract

Developmental delay and spontaneous locomotor activity changes, as well as the reversibility of these adverse effects are apical endpoints used in chemical safety evaluations. These endpoints were assessed at sublethal concentrations in C. elegans using 5-fluorouracil (5FU), hydroxyurea (HU), or ribavirin (RV), teratogens that are associated with reduced fetal growth in mammals. C. elegans develop from egg to egg-laying adult in about three days. Synchronized cohorts were exposed either continuously, or for 24 h (early-only) from first-feeding after hatching. Developmental delays were dose-responsive for all three chemicals in both exposure schemes. For 5FU and HU, developmental delays and hypoactivity levels were similar in continuous and early-only exposure groups, consistent with irreversible developmental effects. The observed hypoactivity in developing C. elegans may be related to reported 5FU-induced muscle impairment and HU-induced post-exposure effects on locomotion parameters in mammals. In contrast to 5FU- and HU-induced hypoactivity, RV was associated with a non-significant trend to slight hyperactivity in both exposure schemes. Continuous RV exposures induced delays to sequential developmental milestones that increased with exposure duration. RV-induced delays were significantly reduced but not eliminated in early-only exposure cohorts, consistent with cumulative RV effects on developmental progress. These findings suggest that C. elegans may be a useful model for detecting chemicals with irreversible, reversible, and/or cumulative effects on organismal development.