title: In vivo radiosensitizing effect of the adenovirus E1A gene in murine and human malignant tumors.
abstract: 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.
authors.affiliation: Department of Pathology, Clinica Puerta de Hierro, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Martin-Duque
authors.forename: R
authors.initials: R
authors.lastname: Sánchez-Prieto
authors.forename: J
authors.initials: J
authors.lastname: Romero
authors.forename: A
authors.initials: A
authors.lastname: Martinez-Lamparero
authors.forename: S
authors.initials: S
authors.lastname: Cebrian-Sagarriga
authors.forename: J
authors.initials: J
authors.lastname: Guinea-Viniegra
authors.forename: C
authors.initials: C
authors.lastname: Dominguez
authors.forename: M
authors.initials: M
authors.lastname: Lleonart
authors.forename: A
authors.initials: A
authors.lastname: Cano
authors.forename: M
authors.initials: M
authors.lastname: Quintanilla
authors.forename: S
authors.initials: S
authors.lastname: Ramón Y Cajal
mesh_terms: 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
chemical_list: D017500:Adenovirus E1A Proteins; D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin