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Related Experiment Videos

Human colonic stem cell mutation frequency with and without irradiation

F Campbell1, C E Fuller, G T Williams

  • 1Department of Pathology, University of Wales College of Medicine, Heath Park, Cardiff, U.K.

The Journal of Pathology
|November 1, 1994
PubMed
Summary

Radiation exposure increases the frequency of discordant crypts in the colon, supporting the theory that these arise from somatic mutations in individuals with specific O-acetylated glycoprotein phenotypes.

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Area of Science:

  • Gastroenterology
  • Molecular Biology
  • Genetics

Background:

  • Mild periodic acid-Schiff (mPAS) staining differentiates O-acetylated from non-O-acetylated sialoglycoproteins.
  • Human colonic mucosa exhibits three phenotypes based on mPAS staining, determined by a single autosomal gene (oat).
  • Discordant crypts, rare in children, are hypothesized to result from somatic mutations in heterozygous adults.

Purpose of the Study:

  • To investigate the role of somatic mutation in the development of discordant colonic crypts.
  • To determine if radiation exposure influences the frequency of discordant crypts.

Main Methods:

  • Comparison of mPAS staining in colonic mucosa from rectal cancer patients who received radiation therapy versus matched controls.
  • Analysis of discordant crypt frequency, classified as wholly or partially involved by aberrant phenotypes.

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  • Examination of historical radiotherapy cases and comparison with mouse models of mutagen-induced somatic mutation.

    • Main Results:

    • Irradiated patients showed a significantly higher frequency of discordant crypts compared to non-irradiated controls (14.5 ± 8.2 x 10⁻⁴ vs. 6.1 ± 4.2 x 10⁻⁴).
    • The increase in discordant crypts was most pronounced in partially involved crypts following radiation (7.5 ± 4.5 x 10⁻⁴ vs. 0.3 ± 0.5 x 10⁻⁴).
    • Historical radiotherapy cases exhibited high discordant crypt frequencies, with a notable proportion of partially affected crypts.

    Conclusions:

    • Radiation exposure acts as a mutagen, increasing the rate of somatic mutation in colonic crypts.
    • The findings support the hypothesis that discordant crypts arise from somatic mutations in heterozygous individuals.
    • The study provides evidence for radiation-induced somatic mutations contributing to phenotypic changes in colonic crypts.