Mechanism of chemotherapeutic drug action in mouse vaginal epithelium

The mouse vaginal assay was modified to study mechanisms of drug action in epithelial cells in relation to the cell cycle. An evaluation of the labeling index, mitotic index, and the percent labeled mitoses in the vaginal epithelium was used to determine the site of drug action in the cell cycle. Systemic absorption from the vaginal epithelium was also monitored by these same measurements in rectal mucosa. Thirty drugs was tested; 17 showed cell kinetic perturbations in the vaginal mucosa and four of these had both vaginal (local) and rectal (systemic) effects. Thirteen drugs had no effect, suggesting inadequate concentration, penetration, duration of drugs exposure, or lack of biochemical action. These 30 drugs were tested in concentrations and vehicles also used for topical screening in psoriatic patients. Only 15 of the 30 drugs tested in this model predicted the clinical results.