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Thursday 16 August 2007

Primary lymphocytes as predictors for species differences in cytotoxic drug sensitivity.

By: Hassan SB, Haglund C, Aleskog A, Larsson R, Lindhagen E.

Toxicol In Vitro 2007 Sep;21(6):1174-81

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.

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