Zebrafish tp53 knockdown extends the survival of irradiated zebrafish embryos more effectively than the p53 inhibitor pifithrin-alpha.
Cancer treatment strategies using radiation therapy have significantly improved outcomes in patients. Although advances in physics and electronics have enabled physicians to plan and deliver radiotherapy regimens precisely and efficiently, studies of the underlying molecular mechanisms of the radiation response could enable more effective and less toxic treatment strategies, as well as protection against radiation damage following unplanned exposure. Using the developing zebrafish embryo as a model system, we hypothesized that knockdown of tp53 mRNA or small molecule inhibition of p53 could alter the efficacy of radiotherapy against developing zebrafish embryos as a model for tumors. We found that interfering with p53 expression and function using hydroxylprolyl-phosphono peptide nucleic acid oligomers or pifithrin-alpha protected developing zebrafish embryos against radiation damage, consistent with our hypothesis.
Duffy
Kevin T
KT
Department of Biochemistry and Molecular Biology and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Wickstrom
Eric
E
D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000528:radiation effects*; D023421:Models, Animal; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010641:Phenotype; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D015996:Survival Rate; D014050:Toluene / Q000031:analogs & derivatives* / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology*
D052160:Benzothiazoles; D009838:Oligodeoxyribonucleotides; D011838:Radiation-Sensitizing Agents; D016159:Tumor Suppressor Protein p53; C505966:hydroxyprolyl-phospho peptide nucleic acid antisense oligonucleotide; D014050:Toluene; C121565:pifithrin