Uridine uptake inhibition as a cytotoxicity test: correlations with the Draize test

The effects of 25 xenobiotic chemicals on the uptake of [3H]-uridine by Balb/c 3T3 cells were assessed. The test compounds, which included alcohols, ethers, esters, ketones, amides, acids and a detergent, inhibited uridine uptake at concentrations lower than those required to kill the cells; thus uridine uptake inhibition is a more sensitive indicator of toxic action than is cell lethality. The concentration of agent required to induce a 50% inhibition in uridine uptake rates after 4 h of treatment was determined for each agent, and this value (UI-50) was used to rank the potency of the test agents. This ranking correlated well with published data on the chemicals' capacity to induce ocular irritation in rabbits (the Draize test). Combinations of agents with differing functional groups produced additive uridine uptake inhibitory effects, suggesting the utility of this approach for the analysis of mixtures. Cells treated with levels of agents that reduced uridine uptake by 60-80% were able to recover most of their uridine uptake capacity after refeeding, indicating that the test shares with in vivo tests the ability to demonstrate recovery from toxic insult. This uridine uptake assay system provides a quantitative and rapid method for assessing toxicity that correlates well with Draize test results.