Multiple CT Scans Extend Lifespan by Delaying Cancer Progression in Cancer-Prone Mice

Radiat Res. 2017 Oct;188(4.2):495-504. doi: 10.1667/RR14575.1. Epub 2017 Jul 25.

Abstract

Computed tomography (CT) scans are a routine diagnostic imaging technique that utilize low-energy X rays with an average absorbed dose of approximately 10 mGy per clinical whole-body CT scan. The growing use of CT scans in the clinic has raised concern of increased carcinogenic risk in patients exposed to ionizing radiation from diagnostic procedures. The goal of this study was to better understand cancer risk associated with low-dose exposures from CT scans. Historically, low-dose exposure preceding a larger challenge dose increases tumor latency, but does little to impact tumor frequency in Trp53+/- mice. To assess the effects of CT scans specifically on tumor progression, whole-body CT scans (10 mGy/scan, 75 kVp) were started at four weeks after 4 Gy irradiation, to allow for completion of tumor initiation. The mice were exposed to weekly CT scans for ten consecutive weeks. In this study, we show that CT scans modify cellular end points commonly associated with carcinogenesis in cancer-prone Trp53+/- heterozygous mice. At five days after completion of CT scan treatment, the multiple CT scans did not cause detectable differences in bone marrow genomic instability, as measured by the formation of micronucleated reticulocytes and H2AX phosphorylation in lymphoid-type cells, and significantly lowered constitutive and radiation induced levels of apoptosis. The overall lifespan of 4 Gy exposed cancer-initiated mice treated with multiple CT scans was increased by approximately 8% compared to mice exposed to 4 Gy alone (P < 0.017). Increased latency periods for lymphoma and sarcoma (P < 0.040) progression contributed to the overall increase in lifespan. However, repeated CT scans did not affect carcinoma latency. To our knowledge, this is the first reported study to show that repeated CT scans, when administered after tumor initiation, can improve cancer morbidity by delaying the progression of specific types of radiation-induced cancers in Trp53+/- mice.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Carcinogenesis / radiation effects
  • Disease Progression
  • Disease Susceptibility
  • Dose-Response Relationship, Radiation
  • Female
  • Histones / metabolism
  • Male
  • Mice
  • Neoplasm Staging
  • Neoplasms, Radiation-Induced / etiology*
  • Neoplasms, Radiation-Induced / metabolism
  • Neoplasms, Radiation-Induced / pathology*
  • Reticulocytes / pathology
  • Reticulocytes / radiation effects
  • Risk Assessment
  • Survival Analysis
  • Tomography, X-Ray Computed / adverse effects*
  • Tumor Suppressor p53-Binding Protein 1 / deficiency
  • Tumor Suppressor p53-Binding Protein 1 / metabolism

Substances

  • Histones
  • Trp53bp1 protein, mouse
  • Tumor Suppressor p53-Binding Protein 1
  • gamma-H2AX protein, mouse