Growth slow-down and growth arrest of human colon carcinoma cells HCT-8 in vitro after exposure to 5-fluoro-2'-deoxyuridine

Abstract. Cellular heterogeneity in drug response denotes a mixed response among individual cells in a drug treated population. Individual cell responses may be more complex than 'cell kill'and 'no response'. In this study we employed a colony formation assay and high-resolution image analysis to detect the various responses such as immediate and delayed cessation of growth, growth delay and growth slow-down, at the level of the individual colony. The evaluation was carried out using a human ileocaecal adenocarcinoma cell line (HCT-8) and the anti-tumour agent 5-fluoro-2'-deoxyuridine (FdUrd). In the presence of a drug concentration which, in standard monolayer assays, inhibits the growth to about 50% (IC₅₀) only about 20% of the colonies ceased to grow and the remaining colonies grew at a growth rate of about 70% of control. At an FdUrd concentration which, in standard monolayer assays, reduced growth by >90% (>IC₉₀), about 50% of the cells grew, with growth rates of about 30% of control. The slowing of growth, most prominent at lower drug concentrations, should be considered in determining mechanisms of drug action at the individual cell level. In clinical situations in which high drug doses are precluded by toxicity to normal tissues, growth slow-down may play a significant role in tumour response.