The intestinal epithelium is constantly exposed to a wide variety of substances in food. Some of these compounds generate aggressive radicals. The cells making up the epithelium tissue have various ways of neutralising radicals. If these defence methods are ineffective, oxidative stress occurs. The Dutch researchers concentrated on the results of this reaction and chose to study the human cell line Caco-2 of intestinal cancer because this type of cell goes through the complete cycle from germ cell to functional cell.
Under the microscope, 20 percent of these cells were seen to kill themselves within four hours when exposed to a mild dose of compounds which produce radicals (25 micromolar). Closer observation showed that in the Caco-2 cell line the p53 gene, which has a key position in the "suicide series", is damaged. However, oxidative stress also leads to the choice of other suicidal routes in which cells which commit suicide have been only slightly affected by oxidative stress. In these undamaged cells, the level of glutathione, a substance which protects the cell against radicals, has hardly decreased at all. This shows that cells which commit suicide undergo subtle changes specifically in their genetic regulation. Evidence has been found that the balance between phosphorylation and dephosphorylation of proteins involved in cell division has shifted in favour of phosphorylation. It is possible that oxidative stress forces a cell to divide at a point when it is not yet ready to do so. Premature division disrupts the further metabolism of the cell and leads to its self-elimination.
Further information:
Jurgen Karczewski (Nijmegen University)
Tel +31 24 345 1116,
Fax +31 24 354 1802,
E-mail jurgenk@xs4all.nl.