CHARACTERIZATION OF A FLUOROURACIL-RESISTANT HUMAN GASTRIC-CARCINOMA CELL-LINE AND ITS MORPHOLOGICAL BEHAVIOR

A fluorouracil (FU)-resistant human carcinoma cell line (SGC-7901/R) was established in culture by progressively increasing the concentration of FU from 50 ng . ml-1 to 2. 5 mg . ml-1. The cell line has been successfully subcultured for more than 150 passages during more than 2 years. Its degree of FU resistance was 139-fold vs that of FU sensitive cell line (SGC-7901/S), and the resistant phenotype was stable when cells were cultured for 23 passages in FU-free medium. The doubling time was 17.3 and 25.6 h for resistant cells and parental cells , respectively. Swiss (nu/nu) nude mice were used for the in vivo experiment, the FU-resistant cell line also exhibited resistance to FU and cross-resistance to mitomycin C. FU inhibited markedly the incorporation of [H-3]UR into sensitive cells and only showed a 31.6% inhibition with FU 100 mug . ml-1 in resistant cells. For the incorporation of [H-3]TdR into DNA, inhibitory rates were seen with different concentrations of FU in resistant cells. By morphologic observation, SGC-7901/R cells showed little secretion but without any tendency to glandular pattern. Their nuclei were allotype with enlarged perinuclear space and a few intranuclear pseudoinclusions. The mitotic phase of cells was found frequently. The phenotype of resistant cell line can be deduced more malignant than that of parental cell line.