, 1997). The mechanism by which acridine and thiazolidine derivatives act has been continuously researched. Thiazolidine derivatives activate peroxisome proliferator-activated receptors (Barros et al., 2010). Meanwhile, acridine derivatives used in cancer chemotherapy have biological targets, such as DNA topoisomerases I and/or II, telomerase/telomeres and kinases (Castillo-González et al., APO866 in vivo 2009, Guo et al., 2009 and Oppegard et al., 2009). Our understanding of ATZD’s cytotoxic mechanisms have been limited to results from double stranded-DNA biosensors and single stranded-DNA solutions, which show a positive interaction

with these ATZD that couple acridine and thiazolidine (Barros et al., 2012). Here, we demonstrate that ATZD inhibit DNA topoisomerase I activity. The cytotoxicity of DNA topoisomerase I inhibitors is caused by blocking DNA topoisomerase I cleavage complexes or by inhibiting DNA topoisomerase I catalytic activity. Then, DNA topoisomerase I inhibitors work by stabilising the DNA topoisomerase I cleavage complexes, which cause DNA damage (Hsiang et al., 1989, Pommier et al., 1998 and Stewart et al., 1998). Because malignant cells often contain greater amounts of DNA topoisomerase I than normal cells, tumour cells should be more sensitive to the

toxic effects of these inhibitors. The malignant cells that often contain great amounts of DNA topoisomerase I include colon adenocarcinoma, several types of non-Hodgkin’s Cytidine deaminase lymphoma, leukaemias, melanoma and carcinomas of the stomach, breast EPZ015666 purchase and lung (Potmesil, 1994). This partially explains the selective cytotoxic effects of ATZD. However, the exact mechanism of this selective antitumor activity remains to be determined. Previous studies have reported that some acridine and thiazolidine derivatives are somatic- and germ-cell mutagenic agents capable of inducing both numerical and structural chromosome aberrations in vitro and in vivo (Attia, 2008, Attia, in press, Kao-Shan et al.,

1984 and Nishi et al., 1989). These compounds are highly cytotoxic/genotoxic to normal lymphocyte cells. Therefore, to improve our understanding of the ATZD’s cytotoxic actions, we assessed their genotoxic effects in human peripheral lymphocytes. Previously, the cytotoxicity of these compounds was assessed against normal lymphocyte cells (Barros et al., 2012); however, the genotoxicity had not been investigated. The genotoxic effects of ATZD were determined using an alkaline comet assay and a chromosome aberration assay; the anti-telomerase activity was determined using a pan telomeric probe. In our studies, none of these ATZD agents showed genotoxicity and/or anti-telomerase activity in cultured human lymphocytes at the experimentally tested concentrations.