Carcinogenesis, Vol 18, 2353-2359, Copyright © 1997 by Oxford University Press
M Venturi, RJ Hambly, B Glinghammar, JJ Rafter and IR Rowland
Human faecal waters from 35 healthy non-smoking volunteers (23 from England
and 12 from Sweden) consuming their habitual diet were screened for
genotoxicity by the single-cell gel electrophoresis (comet) assay using a
human colon adenocarcinoma cell line (CACO-2) as the target. Hydrogen
peroxide induced DNA damage was categorized as low, intermediate or high
for tail moments greater than 5, 17 and 32, respectively: 11 samples were
highly genotoxic, four were intermediate, one was low and 19 showed no
activity. Endonuclease III treatment significantly increased DNA damage for
all except the non-genotoxic faecal waters, suggesting that faecal water
genotoxicity may be due, at least in part, to oxidative damage. Faecal
water cytotoxicity has previously been attributed to the bile and fatty
acid content. In the comet assay no DNA damage was induced by deoxycholate
or lithocholate at normal physiological concentrations, suggesting that the
genotoxicity of faecal water was due to other substances. Both bile acids
induced DNA damage above 300 microM, levels often found in patients with
colonic polyps and there was a significant increase in genotoxicity after
endonuclease III treatment indicative of oxidative DNA damage.
ARTICLES
Genotoxic activity in human faecal water and the role of bile acids: a study using the alkaline comet assay
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