A semi-automated system for the assessment of toxicity to cultured mammalian cells based on detection of changes in staining properties.

We have established a semi-automated microtiter-based system for the quantification of dye binding to cultured eukaryotic cells. This system has been applied to the quantitation of toxic activities that disrupt cell monolayers and their neutralization. We have used this background as a basis for developing a detection and characterization system for activities that do not cause such gross toxicity. A prototype system has been established based on three staining procedures which in broad terms assess cellular dehydrogenase activity, and protein, DNA, and RNA content. The activity of several agents affecting cyclic nucleotide metabolism, including cholera toxin, on the staining properties of exposed monolayers has been assessed. Several new categories of cellular response are readily discernible in this latter system indicating that biological activities may be identified on the basis of the pattern of such responses. Since microtiter based systems show considerable potential for automation, it is suggested that the further development of this approach could offer a realistic prospect for numerous forms of toxicity testing on an industrial scale.