Human colonic stem cell mutation frequency with and without irradiation

Abstract

Mild periodic acid-Schiff (mPAS) staining distinguishes O-acetylated from non-O-acetylated sialoglycoproteins. In human colonic mucosa, individuals possess one of three phenotypes: uniformly mPAS-positive (non-O-acetylated), uniformly mPAS-negative (O-acetylated), and negative with infrequent scattered positive crypts. This is due to a polymorphism in a single autosomal gene (oat). Discordant crypts have not been found in children's colons, suggesting that they result from somatic mutation in heterozygous individuals. We now present evidence to confirm this based on a study of radiation-induced changes. Comparison of mPAS staining of large intestinal mucosa from patients given radiation 4 weeks before surgery for carcinoma of the rectum with matched controls receiving surgery alone showed a similar phenotype distribution, but information irradiated patients showed an increased frequency of discordant crypts (irradiated vs. non-irradiated 14.5 +/- 8.2 x 10(-4) vs. 6.1 +/- 4.2 x 10(-4)). When these were classified as wholly or partially involved by the aberrant phenotype, the increase was most marked in partially involved crypts (7.5 +/- 4.5 x 10(-4) vs. 0.3 +/- 0.5 x 10(-4), Mann-Whitney U, P < 0.005). Two patients receiving radiotherapy many years before colectomy showed a very high total discordant crypt frequency but relatively few partially affected crypts. Studies of somatic mutation in colonic or small intestinal crypts following a single dose of mutagen in mice have shown early partial crypt involvement by the mutated phenotype and later complete crypt involvement.(ABSTRACT TRUNCATED AT 250 WORDS)