Morphonuclear characterization of drug resistance by means of digital cell-image analysis: an in vitro assessment.

The prediction of tumor resistance to antineoplastic drugs remains an important challenge in cancer chemotherapy. Several methods have been proposed in this connection, but they present a number of problems such as clinical relevance and applicability. In the present work we put forward an original methodology to assess the drug sensitivity of cancer cells. For this purpose we submitted chemosensitive and chemoresistant cell lines to different anticancer drugs and monitored the cell growth and the drug-induced morphonuclear effects by means of digital cell-image analysis of Feulgen-stained nuclei. The results showed that drug-induced effects at the morphonuclear level correlated statistically with the effects produced at the cell proliferation level. For example, the mean nuclear size value increased as a function of the drugs' efficiency recorded at the cell proliferation level. In the same way, the frequency of large dense chromatin clumps also increased in accordance with the drugs' efficiency. The present work thus demonstrates that digital cell-image analysis can be applied to monitor the efficiency of chemotherapeutic treatment carried out on cell lines in vitro. The present methodology could possibly be used on solid tumors, from which biological material can be obtained serially by means of fine-needle aspiration. As evidence of this, the present methodology can also be applied to hematological cancers.