Expression of CYP2A6 in turner cells augments cellular sensitivity to tegafur

To examine the role of cytochrome P450 2A6 (CYP2A6) in the cellular sensiti vity to an anti-tumor prodrug, tegafur (FT), a CYP2A6 cDNA construct was tr ansfected into cells of a colon cancer cell line, DLD-1, CYP2A6-expressing cells (DLD-1/CYP2A6 cells) more efficiently catalyzed the conversion of FT to 5-fluorouracil (5-FU) (2.6-fold) and the 7-hydroxylation of coumarin (7. 9-fold) than cells transfected with a null construct (DLD-1/null cells). Th ese results indicated that the expressed CYP2A6 was functionally active. Th e extent of growth inhibition of the DLD-1/CYP2A6 cells by FT was greater t han that of DLD-1/null cells; the difference between the DLD-1/CYP2A6 and D LD-1/null cells was statistically significant at the concentrations of 250, 500 and 1000 muM. 5-FU, an active metabolite of FT; inhibited the grow th of both types of cells to the same extent. Thus, intracellular expression o f CYP2A6 can sensitize cells to FT.