Multiparametric evaluation of the toxic responses of normal human cells treated in vitro with different classes of environmental toxicants

L. E. Allred, J. W. Oldham, G. E. Milo, O. Kindig, C. C. Capen

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Abstract

Eight compounds representing three classes of chemicals were evaluated for their toxic effects of normal neonatal human foreskin fibroblasts in vitro. A battery of toxicity assays were employed to measure the effects of the chemicals on cell viability, DNA synthesis, protein synthesis, DNA repair synthesis, cell ultrastructure, membrane-bound and soluble cytoplasmic proteins, and the activities of six enzymes: β-glucuronidase, acid phosphatase, γ-glutamyl transpeptidase, alkaline phosphatase, 5'-mononucleotidase, and calcium-magnesium activated (Na+,K+)-dependent ATPase. The compounds evaluated included two antibiotics, each with a metabolic derivative-sulfamethazine (SMZ) and acetylsulfamethazine (ASZ), and carbadox (CBX) and desoxycarbadox (DCX); two anthelmintics - haloxon (HAL) and sansalid (SAN); and a steroid with a metabolic derivative, 17α-estradiol (17-AE) and 17α-estradiol-17-β-D-glucoside (AE-G). Compounds with similar biological functions often elicited different patterns of response in the normal human fibroblasts. For example, the two anthelmintics, HAL and SAN, were similar to each other in that they induced 50% relative cloning efficiencies (EC50) at approximately the same concentrations (HAL = 52 μg/ml, SAN = 58 μg/ml), and neither inhibited protein synthesis. They differed, however, in their effects on DNA synthesis. SAN did not inhibit DNA synthesis, while HAL was a profound inhibitor of DNA synthesis (98% inhibition after 4 h at 100 μg/ml). Because the various toxicants elicited such a variety of response patterns as measured by a multiplicity of parameters, we conclude that similarities in survival responses of cells to closely related toxicants may arise frequently through toxic action of different sites within the cells.

Original languageEnglish (US)
Pages (from-to)143-156
Number of pages14
JournalJournal of Toxicology and Environmental Health
Volume10
Issue number1
Publication statusPublished - 1982

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ASJC Scopus subject areas

  • Toxicology
  • Pollution

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