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Characterization of a resistant human colon carcinoma cell line
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CHARACTERIZATION OF A RESISTANT HUMAN COLON CARCINOMA CELL LINE. W.S. DALTON, D.S. ALBERTS, A.E. CRESS and J. TRENT. ARIZONA CANCER CENTER, TUCSON, ARIZONA
The development of resistance to combination chemotherapy is a major problem in the treatment of advanced neoplastic disease. Using a clonogenic assay, we examined a human colon cancer cell line (WiDr) which was made resistant to mixtoxantrone (obtained from R. Wallace, Amer. Cyanamid Co., Pearl River, N.Y.). Cross-resistance was also observed for the structurally related drug, doxorubicin. The DHAD resistant line remained sensitive to cyclophosphamide, vinblastine, and 5FU; no paradoxical increased sensitivity was observed. Chromosome banding analysis was performed on the WiDr parental and drug resistant cell lines. Results demonstrated a relatively similar modal chromosome number in both parental and drug resistant cultures. However, the drug resistant cells displayed a putative homogeneously staining region (HSR) localized to the short arm of chromosome 7. Preliminary studies indicate that drug uptake was decreased in the drug resistant strain possibly related to cell membrane alterations (studies in progress). These studies suggest that the drug resistance observed for this cell llne is characterized by decreased drug uptake which is possibly related to gene amplification.
189
CHARACTERIZATION OF A RESISTANT HUMAN COLON CARCINOMA CELL LINE. W.S. DALTON, D.S. ALBERTS, A.E. CRESS and J. TRENT. ARIZONA CANCER CENTER, TUCSON, ARIZONA
The development of resistance to combination chemotherapy is a major problem in the treatment of advanced neoplastic disease. Using a clonogenic assay, we examined a human colon cancer cell line (WiDr) which was made resistant to mixtoxantrone (obtained from R. Wallace, Amer. Cyanamid Co., Pearl River, N.Y.). Cross-resistance was also observed for the structurally related drug, doxorubicin. The DHAD resistant line remained sensitive to cyclophosphamide, vinblastine, and 5FU; no paradoxical increased sensitivity was observed. Chromosome banding analysis was performed on the WiDr parental and drug resistant cell lines. Results demonstrated a relatively similar modal chromosome number in both parental and drug resistant cultures. However, the drug resistant cells displayed a putative homogeneously staining region (HSR) localized to the short arm of chromosome 7. Preliminary studies indicate that drug uptake was decreased in the drug resistant strain possibly related to cell membrane alterations (studies in progress). These studies suggest that the drug resistance observed for this cell llne is characterized by decreased drug uptake which is possibly related to gene amplification.
189