Adduction of human p53 gene by fecal water: an in vitro biomarker of mutagenesis in the human large bowel.
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.
Greetham
Hazel L
HL
Medical Research Council Dunn Human Nutrition Unit, Cambridge, UK.
Bingham
Sheila A
SA
Burns
Philip A
PA
D015415:Biomarkers / Q000032:analysis*; D001834:Body Water; D018736:DNA Adducts / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000187:drug effects; D005243:Feces / Q000737:chemistry*; D016158:Genes, p53; D006801:Humans; D007420:Intestine, Large / Q000187:drug effects*; D016296:Mutagenesis; D009153:Mutagens / Q000009:adverse effects*; D016133:Polymerase Chain Reaction
D015415:Biomarkers; D018736:DNA Adducts; D009153:Mutagens; D004259:DNA-Directed DNA Polymerase