CORRELATION BETWEEN CELL KILLING BY CIS-DIAMMINEDICHLOROPLATINUM(II) IN 6 MAMMALIAN-CELL LINES AND BINDING OF A CIS-DIAMMINEDICHLOROPLATINUM(II)-DNA ANTISERUM
- 15 June 1990
- journal article
- research article
- Vol. 50 (12) , 3556-3561
Abstract
The relationship between cell killing and the binding of the anticancer drug cis-diamminedichloroplatinum(II) (cis-DDP) to DNA was studied in six mammalian cell lines. Two of the human cell lines (COV413B) were of the same origin, comprising one sensitive to cis-DDP and the other with induced resistance to the drug. The four other lines, two rodent (RIF-1, Chinese hamster ovary) and two human (A2780, A1847), were unrelated. The cell lines differed in their sensitivity to cis-DDP, as tested in a clonogenic assay. cis-DDP-DNA binding was determined by quantitative immunocytochemistry using an antiserum against cis-DDP-modified DNA. The resistance factors relative to RIF-1, calculated from full survival curves for cis-DDP, were 3.8 .+-. 0.4 for Chinese hamster ovary cells and 8.8 .+-. 0.7 for both A2780 and A1847 lines. Using quantitative immunocytochemistry, the levels of the adduct-specific nuclear staining density compared with RIF-1 cells were 4.8 .+-. 0.2 for Chinese hamster ovary cells, 9.1 .+-. 0.2 for A2780, and 10.0 .+-. 0.1 for A1847 cells, i.e., in good agreement with the resistance factors. In studies with the COV413B cells and their cis-DDP-resistant counterpart COV413B-PtR, immunologically detected adduct levels again correlated closely with resistance factors (correlation coefficient = 0.97). The kinetics of cis-DDP-DNA adduct formation and loss was investigated in RIF-1, A2780, and A1847 cells by the immunocytochemistry technique. Adduct levels after a 1-h incubation with approximately equitoxic doses of cis-DDP increased by 18 to 32% (average, 27%) between 0 and 6.5 h after treatment and then declined. Adduct half-lives in this latter phase did not correlate with the sensitivities of the cells for cis-DDP. These results indicate that the initial level of cis-DDP-DNA binding measured by quantitative immunocytochemistry may be a reasonable predictor of sensitivity to this chemotherapeutic drug.This publication has 28 references indexed in Scilit:
- MECHANISM OF CYTOTOXICITY OF ANTICANCER PLATINUM DRUGS - EVIDENCE THAT CIS-DIAMMINEDICHLOROPLATINUM(II) AND CIS-DIAMMINE-(1,1-CYCLOBUTANEDICARBOXYLATO)PLATINUM(II) DIFFER ONLY IN THE KINETICS OF THEIR INTERACTION WITH DNA1986
- FORMATION AND REPAIR OF DNA INTERSTRAND CROSS-LINKS IN RELATION TO CYTO-TOXICITY AND UNSCHEDULED DNA-SYNTHESIS INDUCED IN CONTROL AND MUTANT HUMAN-CELLS TREATED WITH CIS-DIAMMINEDICHLOROPLATINUM(II)1985
- Adducts of the antitumor drug cis-diamminedichloroplatinum(II) with DNA: formation, identification, and quantitationBiochemistry, 1985
- Immunochemical quantitation of adducts induced in DNA by cis-diamminedichloroplatinum(II) and analysis of adduct-related DNA-unwindingChemico-Biological Interactions, 1985
- INDUCTION AND REPAIR OF DNA CROSS-LINKS IN CHINESE-HAMSTER OVARY CELLS TREATED WITH VARIOUS PLATINUM COORDINATION-COMPOUNDS IN RELATION TO PLATINUM BINDING TO DNA, CYTO-TOXICITY, MUTAGENICITY, AND ANTITUMOR-ACTIVITY1984
- QUENCHING OF DNA - PLATINUM(II) MONOADDUCTS AS A POSSIBLE MECHANISM OF RESISTANCE TO CIS-DIAMMINEDICHLOROPLATINUM(II) IN L1210-CELLS1983
- Antibodies elicited against cis-diamminedichloroplatinum(II)-modified DNA are specific for cis-diamminedichloroplatinum(II)-DNA adducts formed in vivo and in vitro.Proceedings of the National Academy of Sciences, 1982
- IMMUNOCHEMICAL STUDIES OF DNA MODIFIED BY CIS-DICHLORODIAMMINEPLATINUM(II) INVIVO AND INVITRO1981
- A New Mouse Tumor Model System (RIF-1) for Comparison of End-Point Studies23JNCI Journal of the National Cancer Institute, 1980
- MUTAGEN-INDUCED DISTURBANCES IN THE DNA OF HUMAN-LYMPHOCYTES DETECTED BY ANTI-NUCLEOSIDE ANTIBODIES1979