Some studies on the distribution and effects of cyclophosphamide (NSC 26271) in normal and neoplastic tissues

The gross uptake and intracellular distribution of ³²P cyclophosphamide has been studied in normal and neoplastic rat and mouse tissues. Prolonged alkylation of DNA and RNA occurs over periods of 24 hours in the mouse and 48 hours in the rat, and it is suggested that this may involve slow release of active metabolites from a drug macromolecule complex. The survival of cells in pulmonary and sc tumors after cyclophosphamide treatment has been studied in situ using a biochemical assay, and the influence of environmental factors at the tumor site has been assessed. The pattern of drug distribution has been studied in large sc tumors, and in one tumor line the drug concentration achieved has been related to estimated cell survival.