New chemotherapeutic drug sensitivity assay for colon carcinomas in monolayer culture.
Ten previously untreated colon carcinomas were tested for chemotherapeutic drug sensitivity in primary monolayer culture. Colon carcinomas were partly digested to groups of epithelial cells which plated with a mean efficiency of 42 +/- 9% (SE) on a collagen I-bovine serum albumin substrate in serum-free medium, producing patches of tightly adherent epithelial cells. The cultured cells were judged epithelial by the presence of cytokeratins, an epithelial cell surface epitope, junctional complexes, and brush borders. Each carcinoma was plated in 40 to 60 Petri dishes (35 mm), yielding a mean of 28 +/- 8 (SE) colonies per dish (6832 +/- 1952 cells). Drugs tested in duplicate plates were mitomycin C, cisplatin, streptozotocin, and 5-fluorouracil at 0.1, 1, 10, and 100 micrograms/ml, and at 0.1, 1, and 2x the peak tolerated drug concentration in serum. Twenty-four h after plating, any nonadherent cells were removed, and the adherent tumor cells were continuously exposed to the drugs for 3 days. Each drug induced colony lysis in a dose-dependent manner in responsive tumors. Drug-resistant, cycling cells were identified by [3H]thymidine incorporation in colonies which were not lysed by drug treatment. Each of the ten carcinomas exhibited inherent resistance to one or more chemotherapy drugs within the concentration ranges clinically achievable.
Schroy
P C
PC
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Cohen
A
A
Winawer
S J
SJ
Friedman
E A
EA
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D046508:Culture Techniques / Q000379:methods; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D016685:Mitomycin; D008937:Mitomycins / Q000627:therapeutic use; D013311:Streptozocin / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D008937:Mitomycins; D016685:Mitomycin; D013311:Streptozocin; D002945:Cisplatin; D005472:Fluorouracil