Before drug candidates can be tested in human studies, preclinical toxicology studies determine the dose at which the drug candidate has toxic effects. Typically, animals are dosed with the drug candidate until a toxic effect is observed. Using standard light microscope-based histology, the toxic lesions are studied in an effort to explain the toxicological event. If light microscopy does not reveal the nature of the lesion then more in-depth studies using transmission electron microscopy (TEM) are needed.
In a classic example, a cell appears apoptopic under the light microscope. However, upon more careful observation using TEM, it becomes obvious that the cell is in perfect condition, but it contains a large vacuole in which drug material is stored. Without using TEM, one could have concluded that the drug candidate causes cell death. The outcome of the TEM study suggests further studies to determine whether the vacuolization and drug storage is a reversible process.
Microscopes for Toxicology: