Ras oncogene-transformed and nontransformed cell populations are each heterogeneous but respond differently to the chemotherapeutic drug cytosine arabinoside (Ara-C)

Abstract

In order to determine whether the growth of ras oncogene-transformed cells and nontransformed cells was inhibited differently by the chemotherapuetic drug cytosine arabinoside (Ara-C) their growth was analyzed by a novel colony-based assay that is sensitive and appropriate for heterogeneous cell populations. Colonies of nontransformed NIH3T3 cells, or ras oncogene-transformed NIH(ras) cells, were grown in the absence of drug and then divided into subclones. Subclones were allowed to continue to grow in the absence or presence of drug. Growth inhibition was determined by comparing the growth of drug-treated subclones. Colonies of nontransformed cells grown in the absence of the drug displayed a large variation in growth, and when grown in the presence of the drug displayed a large variation in growth inhibition. Colonies of transformed cells also displayed a large variation in the absence and presence of the drug. For each cell line, related subclones were more similar to each other than to unrelated subclones, implying inheritance of growth rates and drug response. For NIH3T3 cells, the growth of subclones in the presence of drug was highly correlated with the growth of related subclones in the absence of drug. However, for NIH3T3(ras) cells the growth of subclones in the presence of drug was not correlated with the growth of related subclones in the absence of drug. Therefore, ras oncogene-transformed and nontransformed cell populations differ in their response to Ara-C.