DNA-damage in human cells treated with the closely related alkylating agents peptichemio, m-l-sarcolysin and melphalan*

Abstract

In vitro experiments were performed on human peripheral leukocytes to compare DNA repair synthesis induced by peptichemio (a multipeptide complex containing m-l-sarcolysin), m-l-sarcolysin and melphalan. The peptide bound m-l-sarcolysin gave rise to maximum DNA repair synthesis at a concentration interval between 1 × 10−5 and 3 × 10−5 M as opposed to a concentration interval of 3 × 10−4 to 1 + 10−3 M for melphalan. The peptide bound m-l-sarcolysin induced DNA repair synthesis at similar molar concentrations to m-l-sarcolysin alone. The difference between melphalan on one hand, and m-l-sarcolysin and peptichemio on the other hand, may reflect a more rapid uptake of the latter substances. Inhibition of 3H-uridine incorporation in human peripheral lymphocytes supports-this hypothesis. The frequency of sister chromatid exchanges in human fibroblasts was significantly higher after treatment with m-L-sarcolysin compared to melphalan, a finding which also indicates that these chemically closely related substances modify the cellular DNA differently. When DNA repair synthesis was induced by u.v.-light and methyl-methane-sulphonate (a monofunctional alkylating agent), no additional DNA repair synthesis was induced, if peptichemio, m-L-sarcolysin or melphalan was added. These results indicate that the repair of lesions induced by melphalan peptichemio, u.v.-light and methylmethane sulphonate is mediated by at least one common controlling enzyme.