Different effects of cyclophosphamide in vivo and phosphamide mustard in vitro on two cell clones of chemically induced mammary carcinoma of the rat.

Two cell clones of a methylnitrosourea-induced rat mammary carcinoma, a hyperdiploid (44 chromosomes, clone A) and a hypertetraploid clone (88 chromosomes, clone B) were cultured and transplanted subcutaneously into three groups of eight rats. Group 1 was treated with 62.6 mg cyclophosphamide/kg, group 2 with 41.8 mg/kg once weekly for 3 weeks. The volume of tumors derived from clone B cells was diminished by the administration of the agent, whereas clone A cell tumors did not respond. Incubation of cells of both clones with phosphamide mustard in vitro showed that cells of clone B are much more sensitive to the activated cyclophosphamide, especially after incubation in low concentrations of 40 microM and 20 microM, than those of clone A. It is concluded that the initial success of cyclophosphamide therapy on chemically induced tumors is due to the different sensitivities of the tumor cell populations.