RAS ONCOGENE-TRANSFORMED AND NONTRANSFORMED CELL-POPULATIONS ARE EACHHETEROGENEOUS BUT RESPOND DIFFERENTLY TO THE CHEMOTHERAPEUTIC DRUG CYTOSINE-ARABINOSIDE (ARA-C)

In order to determine whether the growth of I as oncogene-transformed cells and nontransformed cells was inhibited differently by the chemot herapuetic drug cytosine arabinoside (Ara-C) their growth was analyzed by a novel colony-based assay that is sensitive and appropriate for h eterogeneous cell populations. Colonies of nontransformed NIH3T3 cells , or ras oncogene-transformed NIH(ras) cells, were grown in the absenc e of drug and then divided into subclones. Subclones were allowed to c ontinue to grow in the absence or presence of drug. Growth inhibition was determined by comparing the growth of drug-treated subclones with the growth of related untreated 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 v ariation in growth inhibition, Colonies of transformed cells also disp layed a large variation in the absence acid 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 o f drug was highly correlated with the growth of related subclones in t he absence of drug. However, for NIH3T3(rns) cells the growth of subcl ones in the presence of drug was not correlated with the growth of rel ated subclones in the absence of drug, Therefore, ras oncogene-transfo rmed and nontransformed cell populations differ in their response to A ra-C.