Correlated suppression by 5-bromodeoxyuridine of tumorigenicity and plasminogen activator in mouse melanoma cells.

The decrease of tumorigenicity by mouse melanoma clone B559 after growth in the presence of 5-bromodeoxyuridine (BrdU) has been correlated with a decrease in detectable cellular plasminogen activator. Reduction of both activities occurs after one to two cell divisions in the presence of this thymidine analog and is virtually complete within three to four cell cycles. These changes are fully reversible; four to five cell divisions in the absence of BrdU are sufficient to allow both tumorigenicity and plasminogen activator levels to return to normal. These results support the hypotheses that (a) the expression of a cellular plasminogen activator is closely associated with the transformation of normal to malignant cells and that (b) the suppression of tumorigenicity by BrdU reflects the capacity of this base analog to inhibit the expression of specialized functions which accompany the malignant state.