Sensitivity to anticancer agents in vitro: Standardizing the cytotoxic response and characterizing the sensitivities of a reference cell line

The sensitivity to 22, water-soluble cytotoxic agents has been determined using two clonal derivatives (ATCC CCL2 and CCL2.2) of a human cervical carcinoma cell line. Since membrane ultrafiltration (used to remove biocontaminants from dissolved drugs placed in culture) has the potential to reduce the effective drug concentration by drug adsorption to the filter, the actual in vitro drug concentrations were determined spectrophotometrically. Adsorption to cellulose nitrate/cellulose acetate filters was significant for certain agents and could often be reduced (exception: maytansine) by substituting Teflon filters. In vitro responses were assessed by determining the drug concentration which inhibited tumor cell replication by 80%. Different sensitivities to various anticancer agents were observed, as well as individualized sensitivities to different anticancer agents indicating that populations of tumor cells may be heterogeneous with respect to their sensitivity to anticancer agents. The in vitro drug concentrations required to inhibit cervical cells were compared to the initial concentration of each drug in vivo. This type of analysis was utilized with two primary gynecologic tumor preparations and accurately predicted clinical response.