ATLA::Alternatives to Laboratory Animals

Volume 23, Number 4

Potential of human lung cells for predicting acute cytotoxicity.

ATLA 23, 461-468, July/August 1995

Frank A. Barile, Dale Alexander and Alicia Sookhoo

Department of Natural Sciences, Health Professions Division, City University of New York at York College, Jamaica, NY 11451, USA

SUMMARY

Human fetal lung fibroblasts (HFL1) were studied in culture to evaluate their potential as a screen for cytotoxicity. The cytotoxic concentrations determined in vitro were compared with established human and animal toxicity data. Confluent monolayers were incubated in the absence or presence of increasing concentrations of test chemicals for 24 hours, and the MTT assay was used to assess toxicity. Inhibitory concentrations were extrapolated from concentration-effect curves after linear regression analysis. Comparison of the cytotoxicity data with rodent lethal concentrations and human lethal concentrations obtained from the testing of 50 chemicals in human lung cells, suggests that the experimental IC50 values are as accurate as predictors of human toxicity as the equivalent toxic blood concentrations derived from rodent LD50 tests. In addition, evaluation of the first 15 chemicals reveals no significant differences between results from continuous cell lines of human and rodent origin. Together with a related battery of tests, cell culture procedures have the potential to supplement or replace current animal protocols in screening chemicals for human toxicity.

Keywords: In vitro cytotoxicity, MTT assay, cell culture, human lung fibroblasts