Toshie Ohta

p73 Protein Expression Correlates With Radiation-Induced Apoptosis in the Lack of p53 Response to Radiation Therapy for Cervical Cancer

PURPOSE p73 belongs to the p53 tumor suppressor family of genes and can inhibit cell growth in a p53-like manner by inducing apoptosis or cell cycle arrest. Here, we investigated whether p73 could compensate for impaired p53 function in apoptosis induced by radiation therapy (RT) for cervical cancer. METHODS AND MATERIALS Sixty-eight patients with squamous cell carcinoma of the cervix who received definitive RT combined with (n=37) or without (n=31) cisplatin were investigated. Biopsy specimens were excised from the cervical tumor before RT and after 9 Gy. RESULTS Mean apoptosis index (AI) was 0.93% before RT and 1.97% after 9 Gy with a significant increase (p<0.001). For all patients, there was a significant correlation between p73 expression positivity after 9 Gy and AI ratio (AI after 9 Gy/AI before RT) (p=0.021). Forty-one patients were regarded as the p53-responding group according to the expression of p53 after 9 Gy, whereas the remaining 27 patients were regarded as the p53-nonresponding group. A significant correlation between p73 expression after 9 Gy and AI ratio was observed in the p53-non-responding group (p<0.001) but not in the p53-responding group (p=0.940). CONCLUSION Our results suggest that p73 plays an important role in compensating for the lack of p53 function in radiation-induced apoptosis of cervical cancer.

Correlation between single nucleotide polymorphisms and jejunal crypt cell apoptosis after whole body irradiation.

Purpose: To identify loci concerned with radiosensitivity in a mouse model using single nucleotide polymorphism (SNP) markers. Materials and methods: We subjected 276 second filial generation (F2) mice descended from two inbred mouse strains, radiation-induced apoptosis sensitive C57BL/6JNrs (B6) and radiation-induced apoptosis resistant C3H/HeNrs (C3H), to 2.5 Gy whole-body irradiation. We quantified jejunal crypt apoptosis, performed a genome-wide survey, and identified quantitative trait loci (QTL) associated with radiation sensitivity. We expressed apoptosis levels as an apoptotic score (AS), which was equal to the number of apoptotic bodies divided by the number of crypts. We genotyped the mice for 109 SNP markers. Results: AS values were 97.7 ± 32.9 in B6 mice and 49.0 ± 24.9 in C3H mice (p < 0.01). Genome-wide analysis revealed 8 markers (2 on chromosome 9, 4 on 15, 1 on 17, and 1 on 18) affecting radiation-induced jejunal apoptosis with log odds (LOD) scores ranging from 2.11 – 3.91. We found a significant locus on chromosome 15, which was previously reported by Weil and colleagues. Conclusion: These findings support the view that the radiosensitivity of clinically normal tissue depends on variations in several genes.