Determination of the mechanism of action of anticancer drugs by means of the computer-assisted microscope image analysis of Feulgen-stained nuclei.
The antitumoral effects of 30 drugs was monitored in vitro on three neoplastic cell lines. These 30 drugs belonged to various pharmacological classes which included alkylating agents, antimetabolites, Vinca alkaloids, topoisomerase II inhibitors, and intercalating agents. The aim of the present work is to use the same methodology to characterize the 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 quantitatively describing chromatin patterns were submitted to multivariate (principal-components) analyses, with the canonical transformation of the data. Statistical analysis shows that each pharmacological class 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 their mechanisms of action by means of the quantitative chromatin pattern description of Feulgen-stained nuclei.
Pauwels
O
O
Laboratoire de Pharmacologie Cellulaire, Institut de Pharmacie, Université Libre de Bruxelles, Belgium.
Atassi
G
G
Pasteels
J L
JL
Kiss
R
R
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division; D002467:Cell Nucleus / Q000187:drug effects; D004396:Coloring Agents; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D016208:Databases, Factual; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D007091:Image Processing, Computer-Assisted; D012394:Rosaniline Dyes; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004396:Coloring Agents; C007722:Feulgen stain; D012394:Rosaniline Dyes; D004247:DNA