Secondary bile acid induced DNA damage in HT29 cells: are free radicals involved?
Increased bile acid secretion, as a consequence of a high fat diet, results in the increased production of bile acids that may escape the enterohepatic circulation, and be subsequently metabolised by the colonic micro-flora to form the co-mutagenic and co-carcinogenic secondary bile acids. The potential of the secondary bile acids lithocholate (LOC) and deoxycholate (DOC), to induce DNA damage, in the colonocyte cell line HT29, at physiological concentrations both individually and in a 2:1 ratio was assessed. Results indicated significant levels of DNA damage induced by both bile acids, with LOC having the greater DNA damaging capacity. The potential role of vitamin A, and the antioxidant vitamin E, in reducing this damage was determined, over a range of vitamin concentrations. Both vitamins reduced the bile acid induced DNA damage. Vitamin A displayed a dose response relationship, whereas vitamin E reduced DNA damage close to negative control values at all concentrations above 50 microM. These results indicate a protective role for Vitamins A and E, against the DNA damaging capacity of LOC and DOC.
Booth
L A
LA
Department of Biomolecular Sciences, Liverpool John Moores University.
Gilmore
I T
IT
Bilton
R F
RF
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel / Q000379:methods; D005609:Free Radicals / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D008095:Lithocholic Acid / Q000494:pharmacology*; D000084562:Retinyl Esters; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D002756:Cholagogues and Choleretics; D004224:Diterpenes; D005609:Free Radicals; D000084562:Retinyl Esters; D003840:Deoxycholic Acid; D014801:Vitamin A; D014810:Vitamin E; C009166:retinol acetate; D008095:Lithocholic Acid; D004247:DNA