DNA cross-linking following exposure to cis-platinum in primary and serially passaged cultured cells derived from two murine fibrosarcomas.
We compared the kinetics of the repair of total (ISC plus DPC) cross-links and of proteinase-resistant (ISC) cross-links in cultured cells derived from two murine fibrosarcoma tumors, FSA and NFSA, after treatment with cis-platinum (cis-DDP), using a modification of the alkaline elution technique. The two tumors had previously been characterized for their response to cis-DDP in vivo; FSA cells gradually removed cross-links from their genome, whereas the NFSA cells showed no capacity to repair these lesions. The aim of the present study was to establish whether treatment of cells from these same two tumors grown under controlled culture conditions would affect either the nature of the lesions induced by cis-DDP or the kinetics of repair of these lesions when compared with tumors treated with cis-DDP in vivo. The culture conditions represent two situations: in the first, the cells in culture approximated the proportion of tumor and normal host cells present in vivo, and in the second, the normal host cells had been eliminated by subculturing to produce cultures composed entirely of tumor cells. All cells were exposed to cis-DDP (either 10 or 20 micrograms/ml) for 1 h. The relative amounts of total cis-DDP-induced DNA crosslinks and of ISCs were then determined at various times after treatment. The results show that there was little difference in the behavior of these cultured cells compared to the in vivo response of the tumor from which they were derived. For FSA, each cell culture exhibited a capacity to repair DNA cross-links comparable to that of the tumor in vivo. For NFSA, the passaged cells again paralleled the behavior of that tumor in vivo, although in this case by showing no measurable capacity to repair cross-links. The absence of a significant repair response in the NFSA tumor therefore appears to be an intrinsic characteristic of these tumor cells.
Murray
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Department of Experimental Radiotherapy, University of Texas System Cancer Center, M.D. Anderson Hospital and Tumor Institute, Houston 77030.
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Milas
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D000818:Animals; D002945:Cisplatin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004260:DNA Repair / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005354:Fibrosarcoma / Q000378:metabolism*; D051379:Mice; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D004273:DNA, Neoplasm; D002945:Cisplatin