DETERMINATION OF THE MECHANISM OF ACTION OF ANTICANCER DRUGS BY MEANSOF THE COMPUTER-ASSISTED MICROSCOPE IMAGE-ANALYSIS OF FEULGEN-STAINEDNUCLEI

The antitumoral effects of 30 drugs was monitored in vitro on three ne oplastic cell lines. These 30 drugs belonged to various pharmacologica l classes which included alkylating agents, antimetabolites, Vinca alk aloids, topoisomerase II inhibitors, and intercalating agents. The aim of the present work is to use the same methodology to characterize th e drug-induced effects at several biological levels. The drug-induced modifications were, therefore, monitored by means of the digital cell image analysis of Feulgen-stained nuclei. This methodology enabled the cell cycle kinetics to be studied. Furthermore, the numerical data qu antitatively describing chromatin patterns were submitted to multivari ate (principal-components) analyses, with the canonical transformation of the data. Statistical analysis shows that each pharmacological cla ss of anticancer drugs induces specific modifications to the chromatin patterns. The present study, therefore, shows that it is possible to identify distinct classes of antineoplastic drugs on the basis of thei r mechanisms of action by means of the quantitative chromatin pattern description of Feulgen-stained nuclei. (C) 1997 Elsevier Science Inc.