A small-animal model was developed as a guide to whole-body hyperthermia in cancer patients. Anesthetized DBA/2 mice were secured to a platform, and their hindlimbs were immersed in a 42.3° C water bath for 30-60 minutes. Hindlimb hyperthermia resulted in steady-state rectal and femoral bone marrow and muscle temperatures of 42° C and upper extremity muscle and esophagus temperatures of 41° C. With this hyperthermia technique, the mouse spleen colony assay could be used to quantitate the lethality of hyperthermia and/or cis-dichloro- diammineplatinum(ll) (cis-platinum) on clonogenic bone marrow and leukemia cells. Hyperthermia prior to cis-platinum administration increased c/s-platinum inhibition of leukemia colony formation as much as 2 logs; however, antileukemia synergism was greatest when c/s-platinum administration immediately preceded hyperthermia and no evidence existed of synergism against normal bone marrow colonies. Correlative in vivo drug uptake studies showed a marked increase in leukemia cell uptake of195mR-cis-platinum at elevated temperatures, which suggested a potential mechanism for the apparent antileukemia synergism of c/s-platinum and heat.—JNCI 65; 455-461, 1980.
ASJC Scopus subject areas
- Cancer Research