We propose to study the in vivo effects of microwave hyperthermia, alone or in combination with X-irradiation or chemotherapeutic drugs, on the growth and regression, biochemistry and ultrastructure of five types of murine tumors of different growth rates growing in isogeneic mouse hosts. These tumors represent a unique system in which to evaluate the effects of treatment without regard to immunologic influence of the host. In addition, two types of human tumor growing in athymic nude mice will be studied. These tumors have the additional advantage of being directly applicable to the clinical treatment of human neoplasms. The chemotherapeutic drugs to be studied are: BCNU, CCNU, and the DNA intercalating agents lucanthone, hycanthone and IA-3. The murine tumors to be used are: 3 types of mammary adenocarcinoma designated DBAH, MT2 and dbrB; a spindle cell sarcoma designated TEC; a B-cell lymphoma designated DBA/3. The human tumors are a mammary duct carcinoma and a diffuse type of lymphoma. The responses of these tumors will be evaluated with respect to: 1) regression and regrowth of the tumor volume; 2) cell cycle parameters as determined by (3H)thymidine autoradiography; 3) the size of intracellular nucleotide pools as determined by HPLC; 4) the quantity and quality of cytoplasmic organelles as observed by light and electron microscopy, and cytoskeletal changes such as swelling of mitochondria and dilation of membranes in response to treatments; 5) the rate of DNA synthesis as followed by (3H)thymidine incorporation; 6) nonhistone chromatin proteins as observed by SDS polyacrylamide gel electrophoresis.
The aims of this proposal are to evaluate the effectiveness of the various treatment modalities and combinations, to evaluate the use of microwave hypertheremia in cancer treatment both alone and as a potentiator of ionizing radiation or chemotherapy by sensitizing resistant cells; to continue our exploration of the use of DNA intercalating drugs as radiation and hyperthermia sensitzers; to evaluate the role of thermotolerance development in our experimental tumors treated in vivo with hyperthermia. This proposal represents a continuation of the work which has been ongoing in this laboratory for many years, in relating tumor cell structure and function in tumors undergoing treatment.
