Primary lymphocytes as predictors for species differences in cytotoxic drug sensitivity

• Several in vitro methods have been suggested to predict drug-induced haematotoxicity and species differences; the most commonly used being the clonogenic CFU-GM assay. The aim of the current study was to evaluate whether primary lymphocytes from peripheral blood, assayed with a short-term non-clonogenic assay, could be used to detect species differences in drug sensitivity, and offer an alternative to the CFU-GM assay. The effect of 17 different cytotoxic drugs on lymphocytes from human, dog, rat and mouse was evaluated. A higher sensitivity of human than mouse lymphocytes was seen for topotecan and for 3 of 5 antimetabolites tested. Clear species specificity was also seen for the proteasome inhibitor bortezomib where rodent cells were 50–300 times less sensitive than human cells. Good agreement between our data and published CFU-GM data was observed, suggesting that primary lymphocytes may be a useful model for species difference screening in drug development.

Nyckelord

Animals

Antineoplastic Agents/*toxicity

Cell Survival/drug effects

Cells; Cultured

Dogs

Female

Fluorometry

Humans

Leukocytes; Mononuclear/*drug effects

Male

Mice

Mice; Inbred BALB C

Rats

Rats; Inbred Strains

Species Specificity

Toxicity Tests/methods

MEDICINE

MEDICIN

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)