Chemoresistant cell lines: morphonuclear characteristics and chemosensitivity development during long-term culture

The aims of the present work were first to study the stability of the sensitivity and resistance of various cancer cell lines over the period of one year, and second to attempt to correlate the morphological aspects of the lines with the results obtained. To this end we used one mammary and two human vesical lines, each consisting of three different phenotypes: a primitive phenotype (the sensitive line); a phenotype able to proliferate in the presence of three antineoplastic agents (the resistant line); and a phenotype derived from the resistant line but cultivated in the absence of drugs for more than 50 passages. We studied the stability of these lines not only in terms of their chemosensitivity to drugs, but also from the point of view of the morphological characteristics of their nuclei as described by digital image analysis. The results obtained show that the resistant lines retained their resistance even after treatment by antineoplastic agents had been discontinued. However, in this latter case variations became noticeable in their sensitivity to drugs, variations which shifted the line towards either the sensitive or the resistant phenotype. Results obtained from image analysis show that, for each of the lines studied, the morphological aspects of the continuously treated resistant and sensitive lines were phenotype-specific. However, the resistant lines no longer cultivated in the presence of anti-cancer agents exhibited morphonuclear characteristics varying across those of the other two phenotypes. We attribute these variations to modifications in the quality of the serum used.