The Absorption, Distribution and Excretion of (3)H-Chlorambucil in Rats Bearing the Yoshida Ascites Sarcoma

The distribution of (3)H-chlorambucil following its administration by subcutaneous injection to Yoshida ascites tumour-bearing rats has been examined, in an attempt to elucidate the metabolic fate and mode of action of this drug. Drug uptake into the body tissue was rapid, with a high level of radioactivity being associated with the plasma and ascitic fluid during the initial 6-hour period after treatment. Previous studies in vitro had shown that chlorambucil-resistant cells accumulated less drug than their sensitive counterparts: this discrepancy was also observed after in vivo drug treatment and was reflected in the two-fold difference in extent of binding of tritium to DNA, RNA and protein isolated from the 2 cell strains. These results might in part explain the observed difference in metabolism of chlorambucil by the resistant and sensitive strain of Yoshida ascites sarcoma cells.