USE OF THE COMET ASSAY FOR ASSESSMENT OF DRUG-RESISTANCE AND ITS MODULATION IN-VIVO

Drug resistance is generally considered to be a major impediment to su ccessful cancer chemotherapy, yet it is generally not possible to pred ict the degree or timing of the emergence of tumour resistance in most chemotherapy protocols. Recent developments with the single-cell gel electrophoresis or 'comet' assay for DNA damage at the single-cell lev el suggest that this technique might provide a method for identifying and potentially monitoring tumour cell responsiveness to many anti-can cer agents in situ. In principle, this assay could be applied to any a ccessible tumour being treated with chemotherapeutic agents that cause overt DNA damage. We have investigated that supposition using several rodent and human tumour cell lines exhibiting a spectrum of resistanc e to the DNA strand-breaking drug, etoposide. By assessing cells grown as monolayers, spheroids and xenografted tumours in immunodeficient m ice, we found that the comet assay can provide not only an index of se nsitivity to etoposide, but, additionally, can demonstrate the efficac y (or lack thereof) of multidrug resistance (MDR) reversing agents for cells in vitro, and tumours in vivo.