Cytotoxicity (source code)

= Cytotoxicity

\b[Cytotoxicity] is the capacity of an exposure or agent to damage or kill <biological cells>. Its measurement depends on the cell type, exposure conditions, observation time and endpoint. A test of <cell viability>, membrane damage or metabolic activity records a particular response; it does not by itself identify every mechanism of injury or establish overall <biocompatibility>.

A motivating experiment is <T. Mosmann>'s 1983 <tetrazolium salt> colorimetric assay. Living mammalian cells produced a measurable signal read with a multiwell scanning <spectrophotometer>. The primary paper explicitly notes that the signal depends on cellular activation, permitting studies of survival, proliferation and activation.<Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays by T. Mosmann>[Abstract, living-cell signal, activation dependence and multiwell readout]{ref}

For an original blank-corrected comparison, suppose the treated culture gives <absorbance> $A_t=0.45$, the matched control $A_c=0.85$ and the reagent blank $A_b=0.05$. The relative assay signal is
$$
V=\frac{A_t-A_b}{A_c-A_b}=\frac{0.40}{0.80}=0.50.
$$
Calling this a relative signal states exactly what was calculated. It does not establish that half the cells died. In a linear response model $A-A_b=qN$, either halving viable-cell number $N$ at fixed per-cell response $q$, or halving $q$ with no change in $N$, produces the same result.

A useful experiment therefore compares complementary endpoints and controls for the exposure vehicle, reagent background and direct optical interference. A material-only blank can reveal color or light scattering from the tested substance itself. Independent cell counts or a membrane-integrity measurement address different ambiguities from repeated readings of the same optical signal. Reduced proliferation and cell death should be distinguished when interpreting an apparent cytotoxic response.