Use of drug resistance markers to recover clonogenic tumor cells from occult metastases in host tissues.

A variant of metastatic mouse mammary tumor line 410.4 was produced which is resistant to both 60 microM thioguanine and 3 mM ouabain. Occult tumor cells which result from the metastatic spread of this subline are detected by plating cell suspensions from host tissues in selective media containing thioguanine and ouabain (TO). Only the tumor cells survive and form colonies. Tumor cell colonies were recovered when as few as 6 tumor cells mixed with 1 X 10(6) lymph node cells or normal lung cells were plated in TO. Thus, the method potentially will detect the presence of clonogenic tumor cells when the host tissue contains less than 0.0006% tumor cells. Results suggest that, within 15 min of intravenous injection, less than 10% of the injected cells are clonogenic. In addition, clonogenic tumor cells can be detected in draining lymph nodes prior to the appearance of a palpable tumor implant in the subcutis.