Oxidative DNA Damage by Vitamin A and Its Derivative via Superoxide Generation

Abstract

Recent intervention studies revealed that ␤-carotene supplement to smokers resulted in a higher incidence of lung cancer. However, the causal mechanisms remain to be clarified. We reported here that vitamin A (retinol) and its derivative (retinal) caused cellular DNA cleavage detected by pulsed field gel electrophoresis. Retinol and retinal significantly induced 8-oxo-7,8-dihydro-2-deoxyguanosine formation in HL-60 cells but not in H 2 O 2 -resistant HP100 cells, suggesting the involvement of H 2 O 2 in cellular DNA damage. Experiments using 32 P-labeled isolated DNA demonstrated that retinol and retinal caused Cu(II)-mediated DNA damage, which was inhibited by catalase. UV-visible spectroscopic and electron spin resonance-trapping studies revealed the generation of superoxide and carbon-centered radicals, respectively. The superoxide generation during autoxidation of retinoids was significantly correlated with the formation of 8-oxo-7,8-dihydro-2-deoxyguanosine, although the yield of carbon-centered radicals was not necessarily related to the intensity of DNA damage. These findings suggest that superoxide generated by autoxidation of retinoids was dismutated to H 2 O 2 , which was responsible for DNA damage in the presence of endogenous metals. Retinol and retinal have prooxidant abilities, which might lead to carcinogenesis of the supplements of ␤-carotene.

Influence of a 50 Hz magnetic field and of all-trans‑retinol on the proliferation of human cancer cell lines

“…By contrast, lower ROL concentrations 1-5 µM, which are considered to be within the physiological range for Sertoli cells (52) increased neither reactive species production nor proliferation. On the other hand, in human promyelocytic leukemia cells HL-60 concentrations of 2-5 µM have been reported to induce oxidative DNA damage (53). In the present study a dose as low as 0.5 µM ROL, is enough to induce a proliferative response in human cancer cells.…”

Self-Organization of Silver-Core Bimetallic Nanoparticles and Their Application for Catalytic Reaction

“…Solovieva et al reported that antioxidants, ascorbic acid (Solovieva et al, 2007) and dithiothreitol (Solovieva et al, 2008), exhibit cytotoxicity via H 2 O 2 generation. Relevantly, it has been reported that vitamins A (Murata & Kawanishi, 2000) and E (Yamashita et al, 1998) and catechins (Oikawa et al, 2003) induce DNA oxidation through H 2 O 2 generation during their oxidation. H 2 O 2 is a long-lived reactive oxygen species which plays an important role in biomacromolecular damage induced by various chemical compounds (Kawanishi et al, 2001;Hirakawa et al, 2002).…”

“…These findings showed that the Pt nanoparticles have the highest catalytic activity for H 2 O 2 decomposition in the metal nanoparticles used in this experiment and the activity of Pt nanoparticles is suppressed by modification with Ag. (Yamashita et al, 1998;Murata & Kawanishi, 2000). Indeed, an excess of these antioxidants elevates the incidence of cancer (Nitta et al, 1991;Omenn et al, 1996).…”

PML a target of translocations in APL is a regulator of cellular senescence

“…[107][108][109] An intriguing connection between retinoids and the senescence response is the fact that retinoids promote the formation of reactive oxygen species (ROS) in cells. 110 High levels of ROS can be detected in several types of senescence and treatment with hydrogen peroxide or culturing cells on high oxygen also trigger senescence (for a review see Ref. 111).…”