Chromosomal changes associated with resistance to doxorubicin: correlation with tumorigenicity

Chromosome analysis was performed on Friend leukemia cells sensitive and resistant to doxorubicin. With increasing levels of resistance, increased numbers, of metacentric chromosomes and several chromosomal markers were observed. When sensitive cells were exposed to a toxic dose of doxorubicin, multiple chromosomal breaks were observed in 62% of cells. In contrast, when doxorubicin resistant cells were exposed to cytotoxic concentrations, the pulverization phenomenon was not observed. This striking difference suggests a different mechanism for cytotoxicity in sensitive and resistant cells. Moreover, when logarithmically growing cells were grafted subcutaneously in DBA2 mice, the tumorigenic property was related to the level of doxorubicin resistance.