Background: Thymidine kinase 1 (TK1) and 5'(3')-deoxyribonucleotidase (dNT1) regulate the metabolism of thymidine and its analogs. However, the expression patterns and roles of these enzymes in fluorothymidine (FLT) uptake have not been systemically studied.
Materials and methods: TK1 and dNT1 mRNAs were determined by quantitative PCR in 20 asynchronously growing lung and colon cancer cell lines. [3H]FLT uptake and doubling time were measured.
Results: The TK1/GAPDH values varied from 3.09×10(-3)±6.62×10(-4) to 2.44×10(-2)±8.49×10(-4) and dNT1/GAPDH values from 5.84×10(-4)±4.88×10(-5) to 1.59×10(-2)±1.20×10(-3). The correlation coefficient of TK1/GAPDH versus dNT1/GAPDH was 0.669 (p<0.001). [3H]FLT uptake showed negative moderate correlation with dNT1/GAPDH levels (r=-0.563; p<0.01), but no significance with TK1/GAPDH levels. Doubling time had no relationship with the TK1 or dNT1 expression.
Conclusion: This study profiled correlative expression of TK1 and dNT1 in cancer cell lines, and showed that dNT1 expression determines the lower uptake of FLT, providing a basis for understanding deoxyribonucleotide metabolism.