Philip C. Merker

HOST CONDITIONING IN EXPERIMENTAL CHEMOTHERAPY

The screening of potential anticancer agents against transplantable human tumors in mammals would be virtually nonexistent without procedures for altering the species resistance of animals to heterologous tissues. Whatever information of clinical value results from the study of transplantable human tumors will probably stem directly from the fact that host conditioning has made possible the extensive study of such tumors. I t is sometimes necessary to emphasize this thought in order that the questions raised by discussing variations in conditioning procedures will not obscure the real reason for using a heterologous tumor-host system for experimental chemotherapy, that is, that this tissue was derived from human patients, has retained human characteristics,” and may be more like the human nebplasm in its response to chemical compounds than animal tumors. The development of a test system using transplantable human tumors involves the same principles and procedures important in the development of any tumor-host test ~ y s t e m . ~ Moreover, as with any tumor-host system, confidence in the reliability of test results depends on an awareness and consideration of the influence on these results of variables operating within that system. The atypical variable encountered in assaying human tumors for response to potential anticancer agents is the resistance of mammalian species to grafts of heterologous tissue and the effect on both tumor and host of the agents used to lower that resistance. The objective in conditioning for experimental chemotherapy of transplantable human tumors is to use the least amount of conditioning consistent with maximum growth of the transplant and minimum effect on the host. The agents primarily used for host conditioning are X irradiation-generally 150 r--and/or either cortisone or hydrocortisone. These corticoids possess many metabolic activities in addition to their ability to depress the lymphoid organs and cells important to the defenses of the host to foreign tissue. I n rats receiving doses of cortisone of a magnitude needed for effective conditioning for human tumor growth, interference with metabolism is evidenced by the inability of the animals to gain weight normally and by a reduced tolerance to various chemicals (P. C. Merker, N ! . N. Teller and J. E. Palm, unpublished data; see also Teller et al., “The Human Tumor in Cancer Chemotherapy in the Conditioned Rat,” elsewhere in this monograph). The extent to which the corticoids either directly, by acting with test drugs, or indirectly, by side effects on metabolism, influence experimental chemotherapy results is not