Radiation response of human lung cancer cells with inherent and acquired resistance to cisplatin.
We have derived sublines of three human lung cancer cell lines with acquired resistance to cisplatin. The cisplatin resistant sublines of NCI-H69 (small cell), COR-L23 (large cell), and MOR (adenocarcinoma) show 5.3 fold, 3.1 fold, and 3.8 fold resistance, respectively, determined in a 6-day MTT assay. Although the parent lines show a wide range of glutathione content per cell, the sublines each show similar values to their corresponding parent line. Radiation response curves have been obtained using a soft agar clonogenic assay. Values obtained for the parent lines (95% CL in parentheses) were: NCI-H69: Do = 0.99 Gy (0.87-1.16), n = 2.9 (1.6-5.2), GSH = 14 ng/10(4) cells; COR-L23: Do = 1.23 Gy (1.05-1.49), n = 1.3 (0.7-2.2), GSH = 47 ng/10(4) cells; MOR: Do = 1.66 Gy (1.48-1.88), n = 3.0 (1.9-4.8), GSH = 86 ng/10(4) cells. The cisplatin resistant variants of NCI-H69 and COR-L23 showed 31% and 63% increases, respectively, in Do compared to their parent lines, whereas no change in radiation response was seen in MOR. In this panel of lines, therefore, although there is a correlation between glutathione content and radiosensitivity of the parent cell lines, acquired resistance to cisplatin is not accompanied by increased glutathione content. However, two of the three cisplatin resistant lines do show a significantly reduced radiosensitivity.
Twentyman
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MRC Clinical Oncology and Radiotherapeutics Unit, Cambridge, England.
Wright
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Rhodes
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D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D002945:Cisplatin / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D004351:Drug Resistance; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy*; D008558:Melphalan / Q000494:pharmacology; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D005982:Glutathione Transferase; D005978:Glutathione; D002945:Cisplatin; D008558:Melphalan