Application of Cell Cultures to Toxicology

Abstract

The common conception of cytotoxicity is that the cell is killed by the cytotoxin and the assays employed tend to reflect this. There are, however, several distinct aspects of cytotoxicity, differing in cellular mechanisms, outcome, and, consequently, in the assay of their activity (Freshney, 1904). As requirements for in vitro assays become more demanding, driven by mechanistic studies, economics, and by the desire to reduce animal experimentation, there is a need to look more closely at specific cellular responses to toxins and employ an assay most suited to the type of response that is expected. Cytotoxins may have reversible or irreversible effects, and their effects may be immediate or delayed by up to several weeks. There are major differences between (1) physico-chemical damage, which may produce an instantaneous loss of viability, (2) an environmental or pharmaceutical cytotoxin which may have a slight but progressive effect on metabolism over a period of hours or longer, and (3) a loss of reproductive potential, e.g. as a result of irradiation, which may not be immediately apparent in a reduction in the viability of the cells.