title: An extra copy ofp53suppresses development of spontaneous Kras-driven but not radiation-induced cancer.
abstract: The tumor suppressor p53 blocks tumor progression in multiple tumor types. Radiation-induced cancer following exposure to radiation therapy or space travel may also be regulated by p53 because p53 has been proposed to respond to DNA damage to suppress tumorigenesis. Here, we investigate the role of p53 in lung carcinogenesis and lymphomagenesis inLA-1 KrasG12Dmice withwild-type p53or an extra copy ofp53(super p53) exposed to fractionated total body irradiation with low linear energy transfer (low-LET) X-rays or high-LET iron ions and compared tumor formation in these mice with unirradiated controls. We found that an additional copy ofp53suppressed both Kras-driven lung tumor and lymphoma development in the absence of radiation. However, an additional copy ofp53did not affect lymphoma development following low- or high-LET radiation exposure and was unable to suppress radiation-induced expansion of thymocytes with mutatedKras. Moreover, radiation exposure increased lung tumor size insuper p53but notwild-type p53mice. These results demonstrate that althoughp53suppresses the development of spontaneous tumors expressing KrasG12D, in the context of exposure to ionizing radiation, an extra copy ofp53does not protect against radiation-induced lymphoma and may promote KrasG12Dmutant lung cancer.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, USA.
authors.forename: Everett J
authors.initials: EJ
authors.lastname: Moding
authors.affiliation: Department of Radiation Oncology, Duke University, Durham, North Carolina, USA.
authors.forename: Hooney D
authors.initials: HD
authors.lastname: Min
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, USA.
authors.forename: Katherine D
authors.initials: KD
authors.lastname: Castle
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, USA.
authors.forename: Moiez
authors.initials: M
authors.lastname: Ali
authors.affiliation: Department of Radiation Oncology, Duke University, Durham, North Carolina, USA.
authors.forename: Loretta
authors.initials: L
authors.lastname: Woodlief
authors.affiliation: Department of Radiation Oncology, Duke University, Durham, North Carolina, USA.
authors.forename: Nerissa
authors.initials: N
authors.lastname: Williams
authors.affiliation: Department of Radiation Oncology, Duke University, Durham, North Carolina, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Laboratory of Veterinary Clinical Pathology, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Yongbaek
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Duke University, Durham, North Carolina, USA.
authors.forename: Chang-Lung
authors.initials: CL
authors.lastname: Lee
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, USA; Department of Radiation Oncology, Duke University, Durham, North Carolina, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Kirsch