Transduction of the human deoxycytidine kinase gene in rodent tumor cells induces in vivo growth retardation in syngeneic hosts.
Deoxycytidine kinase (dCK) mediates the phosphorylation of nucleoside analogues that can be used as anti-cancer agents. We examined whether susceptibility of mouse colon carcinoma (Colon 26) and rat gliosarcoma (9L) cells to 1-beta-D-arabiofuranosylcytonsine (AraC), a chemotherapeutic agent, can be increased after the tumor cells were transduced with the human dCK gene. Expression of the dCK gene in both cell lines conferred increased sensitivity in vitro to AraC. Although their proliferation rates in vitro remained the same as those of parental cells, tumor growth of the transduced cells in syngeneic host animals was unexpectedly retarded compared with that of respective parental cells. In contrast, the growth of the transduced cells was not different from that of parental cells, when they were inoculated in T cell-defective nude mice. A histological examination revealed infiltration of eosinophils into the dCK gene-transduced but not into parental Colon 26 tumor. These data suggest that a therapeutic gene, when expressed in xenogenic animals, can be a tumor antigen which is recognized by a host defense system.
Kawamura
K
K
Division of Pathology, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, 260-8717, Chiba, Japan.
Namba
H
H
Bahar
R
R
Miyauchi
M
M
Maeda
T
T
Hamada
H
H
Sakiyama
S
S
Tagawa
M
M
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D003561:Cytarabine / Q000494:pharmacology; D003842:Deoxycytidine Kinase / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018316:Gliosarcoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D003842:Deoxycytidine Kinase