TDG and cancer: We show that inactivation of Tdg in MEFs, but also in ES cells, results in a marked cellular resistance towards 5-FU, which can be complemented by expression of wild-type Tdg. The same inverse correlation between TDG proficiency and 5-FU sensitivity was observed with the human cancer cell line HeLa; TDG overexpression in HeLa cells increased cellular sensitivity to 5-FU treatment, whereas siRNA-mediated TDG knockdown in the same cells provided resistance.