Melphalan-induced chromosome damage in sensitive and resistant human melanoma cell lines

Twelve consecutive treatments of a human melanoma cell line (MM253) with melphalan gave a subline (MM253-12M) which was five times more resistant to melphalan with respect to survival. In contrast to mustard-resistant rodent cells, the MM253-12M line had a higher stemline number than the parent line while growth rate and cell and colony morphology were unchanged. A further melphalan treatment following attempted mutagenesis with UV did not increase resistance. In a comparison of these two lines with two melanoma lines derived from other patients and the rat XC line, resistance was correlated with lower frequency of melphalan-induced chromosome aberrations, determined 48 h after a 4-h exposure to melphalan (3 microgram/ml). In the two cell lines studied, aberration-free metaphase cells from treated culture had fewer chromosomes than untreated cells. DNA synthesis studied in the 4- to 72-h period after treatment was inhibited to the same extent in MM253 and MM253-12M cells at 4 microgram/ml but to a greater extent in the sensitive line at 0.1-1.5 microgram/ml. During the first hour of treatment at 0.1-1.5 microgram/ml, DNA synthesis in MM253 appeared to be enhanced.