Differences in repair of DNA cross-links between lymphocytes and epithelial tumor cells from colon cancer patients measured in vitro with the comet assay.

Purpose: The more common approach to comet assay studies with cancer patients involves indirect measurement of the effect of antineoplastic drug or radiation regimen by assessing DNA damage in surrogate cells, such as peripheral blood lymphocytes of cancer patients, to predict how tumor cells may be affected. The aim of the present study was to compare the capability of different cells isolated from a series of 23 colon cancer patients to repair the damage induced by a cancer drug. Experimental Design: We adapted the in vitro comet repair assay for nucleotide excision repair to measure the ability of lymphocytes and normal and tumor epithelial colon cells to remove DNA cross-links induced by oxaliplatin. The excision repair rate was measured quantitatively by the tail parameters: tail DNA, tail length, extent tail moment, and olive tail moment. Results: Kruskal-Wallis analysis revealed significant differences in recognition and excision activity between different cell types (P < 0.001) for all the comet parameters studied. Hence, colon cells showed higher recognition and excision activity than lymphocytes and tumor cells displayed the highest repair capability. We found no significant correlation between the repair activity of tumor colon cells and lymphocytes in any of the comet parameters considered. Conclusions: Our data support the view that lymphocyte repair activity is not predictive of the repair ability of the tumor and that lymphocytes cannot act as surrogate cells. (Clin Cancer Res 2009;15(17):5466-72)