Evaluation of the Clastogenicity of SJG-136, A Novel Pyrrolobenzodiazepine DNA Interstrand Cross-linking Agent, in Comparison with Nitrogen Mustard (HN2)

Abstract

Aims: SJG-136 is a new pyrrolobenzodiazepine used as an anticancer drug with high cytotoxicity against a panel of cancer cells and proved to produce interstrand crosslinks in the minor groove of DNA. Methodology: In this work, SJG-136 (SG2000) was tested for its clastogenicity by calculating the rate of chromosomal aberrations (CAs), the mitotic index and the formation of micronuclei (MN) using the Chinese Hamster ovary (CHO) cell line. Results: The results found showed that SJG-136 caused an increasing number of CAs especially chromatid and isochromatid breaks in comparison with nitrogen mustard (HN2) another well established anticancer drug extensively used as a DNA damaging agent, these CAs were shown to persist with time after treating cells with SGj-136. The mitotic index showed a delay in the cell cycle by more than 50% in cells treated with 0.1µM SJG-136 compared to a delay of 30-40% in cells treated with 10µM HN2. The MN test showed a clear increase of binucleated cells with MN with increasing concentrations of SJG-136 or HN2. Conclusion: These findings suggest that SJG-136 appears to be stronger clastogenic agent compared with HN2 with high cytotoxicity and causing high number of CAs and MN.