Neutral red uptake inhibition in adhered and adhering rat hepatoma-derived Fa32 cells to predict human toxicity.
The cytotoxicity of the MEIC (Multicentre Evaluation of In vitro Cytotoxicity) reference chemicals was investigated by measuring the neutral red uptake inhibition in adhered and adhering rat hepatoma-derived Fa32 cells. The adhered cells were seeded and then treated and the adhering cells were treated simultaneously upon seeding. Five of the 44 test chemicals were twofold more toxic in adhering cells; ethylene glycol was 28-fold more toxic and mercuric chloride was 5.2-fold more toxic than in adhered cells. The cytotoxicity of dithiothreitol was altered in the same way as that of ethylene glycol, probably by interacting with calcium. When the neutral red uptake inhibition was compared with human toxicity, the correlation coefficient for adhering cells was almost identical to that obtained previously in human hepatoma-derived Hep G2 cells and slightly higher for adhered cells. The Hep G2 assay was the best acute in vitro assay for the prediction of human toxicity within the MEIC study. An obviously better correlation was obtained when the strong intoxicant mercuric chloride was withdrawn from the comparison, both for the adhered and the adhering cells. Altogether, the results can be integrated very well with the basal cytotoxicity concept.
Dierickx
Paul J
PJ
Instituut voor Volksgezondheid, Afdeling Toxikologie, Laboratorium Biochemische Toxikologie, Wytsmanstraat 14, B-1050 Brussel, Belgium. p.dierickx@iph.fgov.be
Scheers
Ellen M
EM
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D004229:Dithiothreitol / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007202:Indicators and Reagents / Q000493:pharmacokinetics*; D009499:Neutral Red / Q000493:pharmacokinetics*; D051381:Rats; D012015:Reference Standards; D015203:Reproducibility of Results; D018675:Toxicity Tests / Q000379:methods* / Q000592:standards; D014407:Tumor Cells, Cultured
D007202:Indicators and Reagents; D009499:Neutral Red; D004229:Dithiothreitol