Per os administration of 5-fluorocytosine is effective in the regression of CD-expressing liver metastases in rats.
The bacterial cytosine deaminase (CD) gene, associated to the 5-fluorocytosine (5-FC) prodrug, is one of the more widely used suicide systems in gene therapy. Introduction of the CD gene within a tumor induces, after 5-FC treatment of the animal, a local production of 5-fluorouracil (5-FU) resulting in intratumor chemotherapy. Destruction of the gene-modified tumor is then followed by the triggering of an anti-tumor immune reaction resulting in the regression of distant wild-type metastasis. In pre-clinical studies, 5-FC is generally administered by daily intraperitoneal injections. However, when used as an anti-fungal in humans, either IV or oral administration is used. In this study, we compared oral and intraperitoneal 5-FC administration in rats bearing a wild-type and a cytosine deaminase-expressing liver tumors. The results indicate that per os 5-FC administration is as efficient as intraperitoneal for the induction of CD-expressing tumor regression and the triggering of a distant bystander effect, acting on wild-type liver tumor and extra-hepatic metastasis.
Gavelli
Adolfo
A
Unité INSERM 364, Faculté de Médecine, 06107 Nice cédex 2, France.
Baqué
Patrick
P
Brossettej
Nicole
N
Bourgeon
André
A
Staccini
Pascal
P
Rossi
Bernard
B
Pierrefite-Carle
Valérie
V
D000284:Administration, Oral; D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage; D019496:Cancer Vaccines / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D043525:Cytosine Deaminase / Q000096:biosynthesis* / Q000235:genetics; D005437:Flucytosine / Q000008:administration & dosage*; D015316:Genetic Therapy / Q000379:methods*; D007263:Infusions, Parenteral; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008175:Lung Neoplasms / Q000556:secondary; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D051381:Rats
D000963:Antimetabolites; D019496:Cancer Vaccines; D005437:Flucytosine; D043525:Cytosine Deaminase