PHARMACOKINETIC STUDIES OF A TRANSPLANTABLE MURINE RENAL ADENOCARCINOMA

Abstract

An animal model to investigate new therapeutic approaches for the treatment of renal adenocarcinoma was further studied. This model is based on a transplantable mouse renal adenocarcinoma whose growth follows Gompertzian kinetics, relates to tumor RNA and DNA content and also correlates with the rate of tumor DNA synthesis. This model in the current study was also evaluated for the ability of various therapeutic agents to inhibit tumor DNA synthesis. Such tests may be valuable for the preclinical screening of potentially useful drugs and may provide insight into fundamental aspects of tumor control. CCNU [1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea] and BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] and adriamycin were potent inhibitors of tumor DNA synthesis whereas cytosine arabinoside, bleomycin and cyclophosphamide were not. These observations were confirmed by autoradiography and correlated with other experimental endpoints of tumor therapy such as tumor weight and animal survival. This preclinical screening model is an effective and helpful means, whereby new drugs and drug combinations can be tested for potential use in human renal cell carcinoma.