DIFFERENTIAL CYTO-TOXICITY AND DNA CROSS-LINKING IN NORMAL AND TRANSFORMED HUMAN-FIBROBLASTS TREATED WITH CIS-DIAMMINEDICHLOROPLATINUM(II)

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (7) , 2791-2794
Abstract
DNA interstrand cross-linking had been found previously to correlate with differences in sensitivity among human cell strains treated with chloroethylnitrosoureas. These differences had been attributed to the presence or absence of a specific DNA repair mechanism. Whether another DNA cross-linking agent, [the antineoplastic drug], cis-diamminedichloroplatinum(II) (cis-Pt), would exhibit analogous differences between cell types was studied. A normal human embryo cell strain (IMR-90) was compared with an SV-40-transformed line (VA-13). Interstrand cross-linking and DNA-protein cross-linking were assayed by alkaline elution. As in the case of chloroethylnitrosoureas, the cytotoxicity differences with cis-Pt correlated with differences in interstrand cross-linking. The relative sensitivity of the cell lines to cis-Pt was reversed. Similar DNA-protein cross-linking levels in the 2 cell lines excluded a difference in cis-Pt uptake or intracellular metabolic drug activation or inactivation prior to DNA interaction. The DNA repair mechanism that prevents interstrand cross-linking by chloroethylnitrosoureas apparently does not prevent interstrand cross-linking by cis-Pt. Interstrand cross-linking by cis-Pt may be prevented by an independent mechanism.

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