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Adduction of Human p53 Gene by Fecal Water: An In vitro Biomarker of Mutagenesis in the Human Large Bowel

¹ Medical Research Council Dunn Human Nutrition Unit, Cambridge, United Kingdom and ² Leeds Institute for Molecular Medicine, St. James's University Hospital, Leeds, United Kingdom

Requests for reprints: Philip A. Burns, Leeds Institute for Molecular Medicine, Wellcome Trust Brenner Building, St. James's University Hospital, Leeds LS9 7TF, United Kingdom. Phone: 44-113-343-8625; Fax: 44-113-343-8431. E-mail: p.a.burns{at}leeds.ac.uk

A polymerase arrest assay was designed to determine sites of adduction in the human p53 gene induced by incubation with fecal water. Significant formation of adducts was observed on p53 DNA after a 2-h incubation in fecal water from 10 of 17 samples studied. Large sample-to-sample variation was observed. The major sites of polymerase termination occurred at nucleotides 3' to guanine residues. Adduct sites coincided with colorectal cancer p53 mutation "hotspots," highlighting the potential carcinogenicity of fecal material. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2681–5)