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

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Abstract
Normal (IMR-90) and SV-40-transformed (VA-13) human embryo cells were treated with antitumor nitrosoureas and the effects on cell viability and cell DNA were compared. All 6 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 4 chloroethylnitrosoureas. Whereas VA-13 cells exhibited dose-dependent interstrand crosslinking, little or none was detected in IMR-90 cells. The IMR-90 cells 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.