Cross-linking of DNA in L1210 cells and nuclei treated with cyclophosphamide and phosphoramide mustard

Phosphoramide mustard, formed from cyclophosphamide in vivo and in vitro, may be the active metabolite of this drug. We have found phosphoramide mustard to be at least 100 times more potent than cyclophosphamide in inhibiting growth of two strains of the L1210 lymphoma in culture. Phosphoramide mustard also produced enlargement of cells, an effect not seen with cyclophosphamide. Phosphoramide mustard significantly increased the amount of cross-linked DNA after incubation with intact LM4 cells or nuclei isolated from these cells. Cyclophosphamide had a similar effect only in the isolated nuclei. These findings strengthen the proposed role of phosphoramide mustard as the active metabolite of cyclophosphamide. The effect of cyclophosphamide on nuclei is unexplained.