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 radiose nsitivity through p53-dependent and independent mechanisms. We have studied the sensitivity of murine (MSC11A5, a sarcomatoid epidermoid carcinoma) an d human (HeLa, human cervix carcinoma) E1A-expressing tumors, in vivo, afte r 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. Dail y fractions of 300 cGy over 3 days, up to a total dose of 9 Gy. Cisplatin w as injected intraperitoneally at a dose of 9 mg per kg of body weight. Afte r gamma-irradiation or intraperitoneal injection of cisplatin, about 30% of the E1A-expressing tumors regressed completely or were associated with a m arked decrease in tumorigenicity over the following weeks. We conclude that malignant tumors, when expressing adenovirus E1A, are very sensitive to tr eatment with DNA-damaging agents, in vivo, regardless of the p53 status of the tumors.