Comparison of effects of doxorubicin and radiation on p53-dependent apoptosis in vivo

The effects of doxorubicin and radiation on apoptosis, p53 expression, and tumor growth in human tumor xenografts were investigated. Human ependymobla stoma (NNE), primitive neuroectodermal tumor (YKP), glioblastoma (KYG) and small cell lung carcinoma (GLS) that are all transplantable to nude mice we re treated with doxorubicin (8 mg/kg) or radiation (1 Gy). The histological study was performed by using TUNEL and p53 staining. Cytotoxic effects of doxorubicin and radiation were compared with no-treatment group by the grow th curves and apoptotic index of tumor to each treatment. In NNE with wild- type p53, doxorubicin induced growth delay of tumors (tumor volume doubling time; 13.7+/-3.3 days in control group vs 30.4+/-1.5 days in doxorubicin g roup), but no growth delay of rumors in KYG and GLS with mutant type p53. W hile radiation-induced apoptosis appeared most frequently at 6 h after irra diation, doxorubicin-induced apoptosis had a tendency to appear later. Furt hermore, although the frequency of doxorubicin-induced apoptosis was lower than that of apoptosis by 1 Gy irradiation, apoptotic cells appeared for ma ny hours after the treatment. Doxorubicin-induced apoptosis may be correlat ed with p53 phenotype because apoptosis was induced only in tumor with wild -type p53, but it appeared less frequently and later than radiation-induced apoptosis.