Effects of cell density on drug-induced cell kill kinetics in vitro (Inoculum effect)

The effects of cell density on drug-induced cell kill kinetics were studied by means of clonogenic assay using 3 human leukaemia-lymphoma cell lines. Mitoxantrone, daunorubicin, doxorubicin, vincristine and bleomycin were progressively less efficacious when cell density increased (positive inoculum effects), whereas the effects of cis-platin and carboplatin were not influenced by cell density. Inoculum effects were related to the kind of chemotherapeutic agents tested, irrespective of the type of cell lines used. Preincubation of mitoxantrone or doxorubicin in the presence of cells in high density resulted in decreases in the cytocidal activity, whereas the effects of bleomycin, vincristine and cis-platin were unaffected. These results show that cell density affects the biological effect of certain chemotherapeutic agents. Inactivation of drugs by high densities of cells partially explains this phenomenon.