Multiparametr1c evaluation of the toxic responses of normal human cells treated in vitro with different classes of environmental toxicants

Eight compounds representing three classes of chemicals were evaluated for their toxic effects on normal neonatal human foreskin fibroblasts in vitro. A battery of toxicity assays was 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, y-glutarnyl transpeptidase, alkaline phosphatase, 5¹-mononucleotldase, and calcium-magnesium activated (Na⁺, K⁺,)-dependent ATPase. The compounds evaluated Included two antibiotics, each with a metabolic derivative- sulfamethazine (SMZ) and acetylsulfamethazlne (ASZ), and carbadox (CBX) and desoxycarbadox (DCX); two anthelmintics-haloxon (HAL) and sansalid (SAN); and a steroid with a metabolic derivative, 17a-estradiol (17-AE) and 17a-estradlol-17-(3-D- glucoslde (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 pg/ml, SAN = 58 pg/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 at different sites within the cells