Host: The Japan Radiation Research Society, Chairman of the 52nd Annual Meeting, Toshiteru Okubo (Radiation Effects Research Foundation)
Aldehyde compounds are known to induce DNA-protein crosslinks (DPCs) at high frequency in the genome. It has been shown that aldehyde compounds also induce other types of DNA lesions such as inter- and intra-strand crosslinks, strand breaks, and base adducts in vitro and in vivo. However, the spectra and yields of DNA lesions induced by aldehyde compounds have not been compared on a quantitative basis. This type of information is crucial for understanding the molecular mechanism of genotoxic effects of aldehyde compounds. In the present study, we analyzed the cell-killing efficiencies of aldehyde compounds and DNA lesions induced by the compounds. HeLa cells were treated with formaldehyde (FA), trans-2-pentenal (PEN), crotonaldehyde (CRA), glutaraldehyde (GA), acrolein (ACR), and chloroacetaldehyde (CAA). Cell survival was analyzed by colony formation. The concentrations that gave 10% cell survival were FA (220 μM), PEN (200 μM), CRA (105 μM), GA (22 μM), ACR (17.5 μM), and CAA (10.5 μM). HeLa cells were treated with these concentrations of aldehyde compounds, and genomic DNA was isolated. The amount of DPCs was measured by Western blotting. The result showed that FA, GA, and PEN induced DPCs very efficiently, whereas ACR, CRA, and CAA induced DPCs with poor to negligible efficiencies. We will analyze the amount of DNA double strand breaks and DNA strand crosslinks. These data will be presented in the meeting.
