THE USE OF CATIONIC LIPOSOMES DC-CHOL DOPE AND DDAB/DOPE FOR DIRECT TRANSFER OF ESCHERICHIA-COLI CYTOSINE DEAMINASE GENE INTO GROWING MELANOMA TUMORS/

An attempt was made to use simple cationic liposomes DC-Chol/DOPE and DDAB/DOPE (DC-Chol is 3 beta (N(N',N'-dimethylaminoethane) carbamoyl) cholesterol, DDAB is dimethyldioctadecyl ammonium bromide and DOPE is dioleoylphosphatidylethanolamine) for transfer of Escherichia coli cyt osine deaminase 'suicide' gene under the control of tissue-specific ty rosinase gene promoter directly into the murine melanoma B16(F10) tumo r. Several repeated intratumoral injections of DNA-liposome complexes followed by intraperitoneal administrations of 5-fluorocytosine, which is converted to 5-fluorouracil, caused strong retardation of murine m elanoma B16(F10) tumor growth and, in some cases, rejection of the pre -established tumor. The inhibition of tumor growth expressed as the in creased survival of mice is better seen in the case of using DNA-DDAB/ DOPE complexes as compared to DNA-DC-Chol/DOPE ones. It seems that the observed therapeutic effect appears to result from several factors: 5 -fluorouracil generation by transfected cells, liposome toxicity (DDAB is more toxic than DC-Chol and hence more tumor cells are killed), in creased transfection efficiency of surviving cancer cells (in this cas e DDAB is a better transfection agent than DC-Chol) and, finally, the bystander effect which causes destruction of cells untransfected with CD gene by easily diffusible 5-fluorouracil.