Acute cytotoxicity testing with cultured human lung and dermal cells

Abstract

An extensive in vitro study with cultured cells was conducted to test the basal cytotoxicity theory. This theory suggests that most chemical injury, at least in vitro, is a manifestation of one or more insults to the basic cellular structures and functions common to mammalian cells. This accounts for the similarity of results in multilaboratory studies. Human fetal lung fibroblasts (HFL1), and human skin fibroblasts (WS1, Detroit551) were studied in culture to evaluate their potential to screen for cytotoxicity. Confluent monolayers were incubated in the absence or presence of increasing concentrations of test chemicals for 24 h, and the MTT assay was used to assess toxicity. Inhibitory concentrations were extrapolated from concentration-effect curves after linear regression analysis. Twenty-nine chemicals were tested with each cell line and the cytotoxicity data compared to rodent and human lethal concentrations. The data suggest that the experimental IC50 values are as accurate predictors of human toxicity as equivalent toxic blood concentrations derived from rodent LD50s. In addition, lung and skin fibroblasts revealed no significant differences among the three cell lines. The results support the conclusion that finite cell lines of human origin have the potential for screening chemicals for human toxicity. In combination with previously published reports, the data suggest that a basal cytotoxic phenomenon may explain the similarity of results among different human cell lines.

Effect of metals on β-actin and total protein synthesis in cultured human intestinal epithelial cells

“…Cells were harvested and radioactivity was measured as previously described (Barile and Cardona 1998; Barnes et al ., 1990). …”

A new small molecule inhibits Streptococcus mutans biofilms in vitro and in vivo

“…Pharmaceutical safety was evaluated by in vitro and in vivo testing. Many studies have shown the strong correlation between in vitro cytotoxicity and in vivo animal experiments (Barile and Cardona ; Dierickx ). In the in vitro experiments, we aimed to assess whether 2‐AI/T in the concentration range that effectively inhibited bacteria biofilm can affect the oral tissues.…”

Effects of the antimycobacterial compound 2-phenoxy-1-phenylethanone on rat hepatocytes and formation of metabolites

“…Cytotoxicity testing is a screening tool that typically uses cell lines for ranking acute toxicities of compounds based on alterations in cellular functions that are common to all mammalian cells (Barile & Cardona, 1998). Several cell lines including metabolically competent cells, such as primary cultured hepatocytes, can be used to detect the biotransformation of molecules and generation of reactive or toxic metabolites (Gómez-Lechón et al, 2001).…”