Differential cytotoxicity and DNA cross-linking in normal and transformed human fibroblasts treated with cis-diamminedichloroplatinum(II)

L. C. Erickson, L. A. Zwelling, Jonathan M Ducore, N. A. Sharkey, K. W. Kohn

Research output: Contribution to journalArticle

51 Scopus citations

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. The current work addressed the question of whether another DNA cross-linking agent, cis-diamminedichloroplatinum(II) (cis-Pt), would exhibit analogous differences between cell types. A normal human embryo cell strain (IMR-90) was compared with an SV40-transformed line (VA-13). Interstrand cross-linking and DNA-protein cross-linking were assayed by alkaline elution. As in the case of chloroethylnitrosureas, the cytotoxicity differences with cis-Pt correlated with differences in interstrand cross-linking. The relative sensitivity of the cell lines to cis-Pt, however, was reversed. Similar DNA-protein cross-linking levels in the two cell lines included a difference in cis-Pt uptake or intracellular metabolic drug activation or inactivation prior to DNA interaction. It was concluded that the DNA repair mechanism that prevents interstrand cross-linking by chloroethylnitrosoureas does not prevent interstrand cross-linking by cis-Pt. Interstrand cross-linking by cis-Pt may be prevented by an independent mechanism.

Original languageEnglish (US)
Pages (from-to)2791-2794
Number of pages4
JournalCancer Research
Volume41
Issue number7
StatePublished - 1981
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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