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Radiation-induced carcinogenesis: studies using human epithelial cell lines

A Riches1, Z Herceg, H Wang

  • 1School of Biological and Medical Sciences, University of St. Andrews, Scotland, United Kingdom. acrl@st-andrews.ac.uk

Radiation Oncology Investigations
|January 1, 1997
PubMed
Summary
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Developing models for radiation-induced carcinogenesis is challenging. The human thyroid epithelial cell line (HTori-3) shows promise as a model, as irradiation induced tumors and p53 mutations were observed.

Area of Science:

  • Oncology
  • Radiation Biology
  • Cell Biology

Background:

  • Studying radiation-induced carcinogenesis in human epithelial cells is difficult.
  • Immortalized human epithelial cell lines offer potential models.
  • Previous models using keratinocyte and embryonic lung cells were unsuitable due to inherent tumorogenicity.

Purpose of the Study:

  • To evaluate the suitability of different human epithelial cell lines as models for radiation-induced carcinogenesis.
  • To investigate the response of human urothelial and thyroid epithelial cells to gamma irradiation in vitro and in vivo.
  • To identify potential molecular events, such as p53 mutations, associated with radiation-induced tumor formation.

Main Methods:

  • Testing the tumorogenicity of un-irradiated human keratinocyte (HPV-G) and embryonic lung (L132) cell lines in T-cell-deficient mice.

Related Experiment Videos

  • Irradiating human urothelial (SV-HUC-1, NT11, BC16) and thyroid epithelial (HTori-3) cell lines with varying doses of gamma radiation (2, 4, 8 Gy).
  • Assessing tumor formation after injecting irradiated cells into mice and analyzing derived thyroid tumor cell lines for p53 mutations using single-stranded conformational polymorphism (SSCP) analysis.

    • Main Results:

    • Human urothelial cell lines were refractory to radiation-induced carcinogenesis, with only one tumor observed.
    • Irradiation of urothelial cells induced changes in anchorage-independent growth at 8 Gy but not lower doses.
    • Irradiation of the human thyroid epithelial cell line (HTori-3) resulted in tumor formation in mice.
    • p53 mutations in exons 5-8 were detected in some cell lines derived from HTori-3 induced thyroid tumors.

    Conclusions:

    • The human thyroid epithelial cell line (HTori-3) is a promising model for studying radiation-induced carcinogenesis.
    • HTori-3 cells can be transformed into tumors following gamma irradiation.
    • p53 mutations are potential molecular events involved in radiation-induced thyroid carcinogenesis using this model.