1.
Andersson, Helén, 1982-, et al.
(författare)
Low levels of the air pollutant 1-nitropyrene induce DNA damage, increased levels of reactive oxygen species and endoplasmic reticulum stress in human endothelial cells
2009
Ingår i: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 262:1, s. 57-64
Tidskriftsartikel (refereegranskat) abstract
Both epidemiological and experimental studies suggest that exposure to high levels of air pollution is a risk factor associated with cardiovascular disease. Traffic emission is a major source of exposure to persistent air pollutants such as nitrated polycyclic aromatic hydrocarbons (nitro-PAHs). 1-Nitropyrene (1-NP), one of the most abundant nitro-PAHs in diesel exhausts, was selected as a model nitro-PAH for the present study. The aim of the study was to investigate the effects of 1-NP in human umbilical vein endothelial cells (HUVECs) and the metabolic pathways involved. The nitroreductase inhibitor dicoumarol and the coplanar aryl hydrocarbon receptor (AhR) ligand PCB 126 were used to modulate the metabolism of 1-NP. The results revealed that low levels (< or =10microM) of 1-NP induced DNA damage, increased levels of reactive oxygen species (ROS) and increased protein expression of the endoplasmic reticulum (ER) stress chaperone GRP78. A decrease in cell viability was only observed following exposure to a higher level of 1-NP (15microM). Inhibition of nitroreductive metabolism by dicoumarol attenuated the induction of DNA damage, intracellular ROS levels and GRP78 expression. This suggests that the effects of 1-NP on HUVEC were mediated by metabolites mainly formed at nitroreduction. Our findings suggest that the human blood vessel endothelium is a sensitive target tissue for the major nitro-PAH constituent in diesel exhaust.
2.
Demma, Jemal, et al.
(författare)
Genotoxicity of plumbagin and its effects on catechol and NQNO-induced DNA damage in mouse lymphoma cells
2009
Ingår i: Toxicology in Vitro. - : Elsevier BV. - 0887-2333 .- 1879-3177. ; 23:2, s. 266-271
Tidskriftsartikel (refereegranskat) abstract
Plumbagin, a naphtoquinone present in the roots of Plumbago zeylanica, has been reported to have many beneficial effects such as antibacterial, antifungal, anticancer, antimutagenic and antioxidant effects, but this compound has also been reported to have many side effects. Given the wide use of P. zeylanica in traditional medicine and the various potential therapeutic uses of plumbagin, the present study was carried out to further elucidate the potential genotoxicity and antigenotoxicity of plumbagin in mouse lymphoma L5178Y cells, using the comet assay. Without affecting the cell viability, plumbagin itself was found to induce significant DNA damage at concentrations as low as 0.25 ng/ml. When the cells were exposed to non-DNA damaging concentrations of plumbagin, together with NQNO (known to interact with DNA in many different ways) or catechol (known to induce oxidative DNA damage), plumbagin was found to significantly reduce the catechol-induced DNA damage, but to be without protective effect against the NQNO-induced damage. The fact that non-DNA damaging concentrations of plumbagin diminished the DNA damage induced by catechol, provides further support for the idea that plumbagin may act as an antioxidative agent at low concentrations.
3.
Demma, Jemal, et al.
(författare)
Potential genotoxicity of plant extracts used in Ethiopian traditional medicine
2009
Ingår i: Journal of Ethnopharmacology. - : Elsevier BV. - 0378-8741 .- 1872-7573. ; 122:1, s. 136-142
Tidskriftsartikel (refereegranskat) abstract
Aim of the study: Although traditional herbal medicines are widely used in Ethiopia, no information is available on their potential genotoxicity. In the present study, hydroalcoholic extracts of Glinus lotoides, Plumbago zeylanica, Rumex steudelii and Thymus schimperi were evaluated for their DNA damaging effects using the comet assay. Material and methods: Mouse lymphoma L5178Y cells were exposed to different concentrations of the extracts for 3 h with and without metabolic activation (S9-mix) using 4-nitroquinoline-N-oxide and benzo(a)pyrene as positive controls, and vehicles as negative controls. Results: In the absence of S9, all extracts were found to induce significant DNA damage without affecting the cell viability. T schimperi and R. steudelii were the most potent DNA-damaging extracts, and G. lotoides and P. zeylanica the least potent. The addition of S9 had different effects on the DNA damage induced by the extracts: it lowered the DNA damaging effect of P. zeylanica, did not affect the DNA damaging effect of T. schimperi, and increased the DNA damaging effects of R. steudelii and G. lotoides. Conclusion: The findings of the present study suggest that all extracts evaluated have a genotoxic potential in vitro which needs to be substantiated by further studies.
