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 ependymoblastoma ( NNE), primitive neuroectodermal tumor (YKP), glioblastoma (KYG) and small cell lung carcinoma ( GLS) that are all transplantable to nude mice were 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 growth 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 group), but no growth delay of tumors in KYG and GLS with mutant type p53. While radiation-induced apoptosis appeared most frequently at 6 h after irradiation, doxorubicin-induced apoptosis had a tendency to appear later. Furthermore, although the frequency of doxorubicin-induced apoptosis was lower than that of apoptosis by 1 Gy irradiation, apoptotic cells appeared for many hours after the treatment. Doxorubicin-induced apoptosis may be correlated 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.[1]References
- Comparison of effects of doxorubicin and radiation on p53-dependent apoptosis in vivo. Hayakawa, K., Hasegawa, M., Kawashima, M., Nakamura, Y., Matsuura, M., Toda, H., Hayakawa, K., Mitsuhashi, N., Niibe, H. Oncol. Rep. (2000) [Pubmed]
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