A comparative cytogenetic study of melphalan-sensitive and -resistant murine L1210 leukemia cells.

A cytogenetic analysis of melphalan-sensitive and -resistant murine L1210 leukemia cells maintained in vivo indicated that the drug-resistant tumor had a modal number of 40 chromosomes while the sensitive tumor possessed a mode of 41 chromosomes. Two marker chromosomes were present in both the sensitive and the resistant tumors. One was of medium length with secondary constrictions, and the other was a minute chromosome. A single in vitro exposure of the sensitive tumor cells to a cytotoxic concentration of melphalan was not accompanied by a change in modal number but resulted in chromatid exchange. No alterations were found in resistant tumor cells which were exposed to the same drug concentration. However, exposure of resistant tumor cells to higher doses of melphalan resulted in chromatid breaks, chromatid gaps and the formation of acentric chromosomes. The resistant tumor, transplanted once without drug injection, maintained a sharp mode of 40 chromosomes.