DNA crosslinking and cytotoxicity in normal and transformed human cells treated with antitumor nitrosoureas

L. C. Erickson, M. O. Bradley, Jonathan M Ducore, R. A. Ewig, K. W. Kohn

Research output: Contribution to journalArticle

179 Scopus citations

Abstract

Normal (IMR-90) and simian virus 40-transformed (VA-13) human embryo cells were treated with antitumor nitrosoureas, and the effects on cell viability and cell DNA were compared. All six nitrosoureas tested were more toxic to VA-13 cells than to IMR-90 cells as measured by decrease in cell proliferation or in colony formation. The nitrosoureas capable of generating alkylisocyanates produced a smaller difference between the cell types than did derivatives lacking this capacity. DNA damage was measured by alkaline elution in cells treated with four chloroethylnitrosoureas. Whereas VA-13 cells exhibited dose-dependent interstrand crosslinking, little or none was detected in IMR-90 cells. The IMR-90 cells, however, exhibited at least as much DNA-protein crosslinking as did VA-13 cells. The results can be interpreted in terms of a possible difference in DNA repair between the cell lines.

Original languageEnglish (US)
Pages (from-to)467-471
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume77
Issue number1
StatePublished - 1980
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • General

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