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Strain difference in transgene-induced tumorigenesis and suppressive effect of ionizing radiation

Bibek Dutta1, Taichi Asami1, Tohru Imatomi1

  • 1Laboratory of Genome Stability, Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 277-8562, Kashiwa, Japan.

Journal of Radiation Research
|November 24, 2020
PubMed

Insights

Transgenic medaka with the xmrk oncogene develop pigment cell tumors. Genetic background and p53 status influence tumor progression, with hybrids showing suppressed malignancy, suggesting tumor suppressors in the HNI strain.

Area of Science:

  • Genetics
  • Oncology
  • Developmental Biology

Background:

  • Transgenic expression of the Xiphophorus oncogene xmrk in medaka, driven by a pigment cell-specific mitf promoter, leads to hyperpigmentation and pigment cell tumors.
  • Medaka fish (Oryzias latipes) are utilized as a model organism for studying cancer development due to their genetic tractability and rapid development.

Purpose of the Study:

  • To investigate the influence of different genetic backgrounds (Hd-rR and HNI inbred strains) and p53 gene status on the progression of pigment cell tumors induced by mitf:xmrk.
  • To evaluate the impact of gamma irradiation on tumorigenesis in xmrk-transgenic medaka across different genetic backgrounds.

Main Methods:

  • Crossbreeding of Hd-rR and HNI medaka strains to create hybrid models with varying genetic backgrounds and p53 genotypes (p53+/-, p53-/-).
  • Induction of hyperpigmentation and tumors using the mitf:xmrk transgene in different medaka genetic backgrounds.
  • Assessment of tumor progression over four months following a single 1.3 Gy gamma irradiation exposure.

Main Results:

  • Tumorigenesis was less frequent in p53+/- fish compared to p53-/- fish on the Hd-rR background.
  • Hd-rR/HNI hybrids exhibited higher incidence of hyperpigmentation but lower frequency of malignant tumors than Hd-rR homozygotes, indicating potential tumor suppressor activity in HNI.
  • Gamma irradiation differentially suppressed hyperpigmentation frequency in purebred Hd-rR compared to hybrids.

Conclusions:

  • Genetic background significantly modulates xmrk-induced pigment cell tumor development in medaka.
  • The HNI genetic background appears to possess tumor suppressor mechanisms that limit malignant progression.
  • Gamma irradiation exerts a variable suppressive effect on hyperpigmentation, dependent on the genetic background of the medaka.
Keywords:
irradiationmedakamitfp53tumorxmrk

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