Studies on formation and repair of formaldehyde-damaged DNA by detection of DNA-protein crosslinks and DNA breaks

Abstract

Formaldehyde (FA) is a genotoxic and mutagenic substance. In 2004, IARC (International Agency for Research on Cancer) concluded that FA is carcinogenic in humans after reevaluating the available evidence on the carcinogenicity of FA. Although many studies have shown that FA had extensive genotoxicity including DNA-protein crosslinks (DPC) and DNA single strand breaks (DSSB), most of these studies only discussed the effects of FA at high levels. In this study, KCl-SDS assay and single cell gel electrophoresis (SCGE) were used to investigate the formation and repair process of FA-induced DPC and DSSB in human peripheral blood lymphocytes and Hela cell lines. KCl-SDS assay was applied to detect DPC induced by liquid FA in human peripheral blood lymphocytes in vitro. The results showed that FA could induce DPC at high levels (> or =50 micro M). By combining the results of KCl-SDS assay and SCGE, it could be determined that FA would induce DNA-DNA crosslinks (DDC) when FA concentration was more than 25 microM. The repair process of FA-induced DPC was studied with KCl-SDS assay in Hela cell lines and the results demonstrated that FA-induced DPC could be significantly repaired after 18 hours. The SCGE was also used to determine FA-induced DSSB and its repair process in Hela cell lines. The results demonstrated that DNA breakages, which is capable of being induced by FA at a low level (<30 microM), enabled to be repaired completely in 90 minutes.