In vivo radiosensitizing effect of the adenovirus E1A gene in murine and human malignant tumors.
The adenovirus E1A gene is a potent inducer of chemosensitivity and radiosensitivity through p53-dependent and independent mechanisms. We have studied the sensitivity of murine (MSC11A5, a sarcomatoid epidermoid carcinoma) and human (HeLa, human cervix carcinoma) E1A-expressing tumors, in vivo, after treatment with cisplatin or gamma-irradiation. In athymic mice, half-body irradiation was performed in an AECL Cobalt unit, at an SSD of 80 cm. Daily fractions of 300 cGy over 3 days, up to a total dose of 9 Gy. Cisplatin was injected intraperitoneally at a dose of 9 mg per kg of body weight. After gamma-irradiation or intraperitoneal injection of cisplatin, about 30% of the E1A-expressing tumors regressed completely or were associated with a marked decrease in tumorigenicity over the following weeks. We conclude that malignant tumors, when expressing adenovirus E1A, are very sensitive to treatment with DNA-damaging agents, in vivo, regardless of the p53 status of the tumors.
Martin-Duque
P
P
Department of Pathology, Clinica Puerta de Hierro, Madrid, Spain.
Sánchez-Prieto
R
R
Romero
J
J
Martinez-Lamparero
A
A
Cebrian-Sagarriga
S
S
Guinea-Viniegra
J
J
Dominguez
C
C
Lleonart
M
M
Cano
A
A
Quintanilla
M
M
Ramón Y Cajal
S
S
D017500:Adenovirus E1A Proteins / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005260:Female; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D017500:Adenovirus E1A Proteins; D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin