Oxygen free radical generating mechanisms in the colon: do the semiquinones of vitamin K play a role in the aetiology of colon cancer?
It is proposed that bile acids (deoxycholic acid), the K vitamins, iron(II) complexes and oxygen interact to induce an oncogenic effect in the colon by the generation of free radicals. In the relatively low oxidising/reducing conditions of the colonic lumen the K vitamins exist in the reduced form; however, if absorbed into the mucosa they have the capacity to be chemically oxidised and to enter into a redox cycle yielding oxygen radicals. The semiquinone radical of K(1) (phylloquinone) has been stabilised in bile acid mixed micelles and investigated by electron paramagnetic resonance spectroscopy and quantum chemical calculations. The estimated half-life of the radical was about 30 min which confirms a remarkably high stability in aqueous micellar solution. A model is presented in which the reduced K vitamins may initiate superoxide radical, O2(-*) generation leading to Fe(II) mediated Fenton reactions in the stem colon cells.
Valko
M
M
Department of Physical Chemistry, Slovak Technical University, Bratislava. mvalko@cvt.stuba.sk
Morris
H
H
Mazúr
M
M
Rapta
P
P
Bilton
R F
RF
D001647:Bile Acids and Salts / Q000737:chemistry; D003106:Colon / Q000737:chemistry / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000209:etiology*; D004032:Diet; D004578:Electron Spin Resonance Spectroscopy; D006207:Half-Life; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism; D008823:Micelles; D008956:Models, Chemical; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011809:Quinones / Q000737:chemistry / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D014812:Vitamin K / Q000737:chemistry / Q000378:metabolism*; D010837:Vitamin K 1 / Q000737:chemistry / Q000378:metabolism
D001647:Bile Acids and Salts; D008823:Micelles; D011809:Quinones; D013481:Superoxides; D014812:Vitamin K; D010837:Vitamin K 1