Photoactive CO-releasing complexes containing iron - genotoxicity and ability in HO-1 gene induction in HL-60 cells.

This paper presents the results of research on the biological properties of two photoactive CO-releasing molecules containing iron, i.e. (η5-C5H5)Fe(CO)2(η1-N-maleimidato) (complex A) and (η5-C5H5)Fe(CO)2(η1-N-succinimidato) (complex B). We studied their cytotoxicity, genotoxicity and the ability of inducing the HO-1 gene in HL-60 cells. We also investigated the kinetics of DNA damage repair induced by complexes A and B. We demonstrated that complex B was not toxic to HL-60 cells in high doses (above 100 μM). The ability to induce DNA damage was higher for complex A. Importantly, there was no difference in irradiated and non-irradiated cells for both complexes. DNA damage induced by complex B was repaired efficiently, while the repair of DNA damage induced by complex A was disturbed. Complex B had a minor effect on HO-1 gene expression (less than 2-fold induction), while complex A had induced HO-1 gene expression to a great extent (over 17-fold for 10 μM) - similarly in irradiated and non-irradiated HL-60 cells. The results of our research indicate that the ability of both complexes to damage DNA and to upregulate HO-1 gene expression is not related to the release of CO. Further research is needed to test whether these compounds can be considered as potential CO carriers in humans.