Screening of Toxic Compounds in Mammalian Cell Cultures

Abstract

The cytotoxic concentrations of about 100 randomly selected drugs and chemicals, tested on HeLa cells in the MIT-24 system and/or in primary cultures of fetal chicken cells, were compared with the lethal doses and/or concentrations of the agents in the mouse and in man. Most agents (80%) had a similar toxicity in vitro and in vivo, suggesting a lethal interference in man with basal functions common to all specialized human tissues as well as cultured cells, i.e., basal cytotoxicity. This high frequency of basally cytotoxic agents opens possibilities for screening chemicals for toxicity and for studying cytotoxic mechanisms with a standard battery of a few appropriate cell tests. This battery may be used in three ways: (1) to study cytotoxic mechanisms of all chemicals, and apply the resulting knowledge to understanding toxicity in man of basally cytotoxic agents; (2) to supplement conventional animal tests in acute toxicity test programs; (3) to screen chemicals and extracts for their potential basal cytotoxicity. To validate these ideas and to select suitable tests for the battery, results from cytotoxicity tests on a wide variety of chemicals in several in vitro systems must be compared with one another and with the toxicity of the agents in animals and man.

Advantages of in vitro cytotoxicity testing by using primary rat hepatocytes in comparison with established cell lines.

“…The dose-response curves of three compounds − acetaminophen, cyclophosphamide and diclofenac sodium − are presented in Fig.1-3. According to IC 50 values in Table 1, the compounds of acetaminophen, cyclophosphamide, diclofenac sodium and disulfiram displayed IC 50 values 2 to 13 times higher in the three cell lines than those in rat primary Almost all of the compounds tested exhibited a rough similarity (differences were generally less than threefold) of IC 50 values in the four cell cultures, which indicates a "basal cytotoxicity" as proposed by Ekwall (1983). It was suggested that for most chemicals, toxicity is a consequence of non-specific alterations in cellular functions.…”

A review on the effects of prebiotics on cell toxicity and integrity

“…[10] Cytotoxicity Cytotoxicity is defined as the negative consequences resulting from disturbance with structures and/or processes required for cell survival, proliferation, and function. [19] This causes cell necrosis (disintegration of membrane integrity) and lysis. The cells may decrease in viability by ceasing growth and dividing or even trigger apoptosis (death of program cell).…”

Sirc-CVS Cytotoxicity Test: An Alternative for Predicting Rodent Acute Systemic Toxicity

“…No animal testing was performed for this study. Following the method described by Evans et al (2001), the lowest LD 50 value of a test chemical that 2) MEIC; Multicentre Evaluation of In Vitro Cytotoxicity (Ekwall et al 1983). …”