DNA damage effect

Leanderson, P. and Tagesson, C. (1989). Cigarette smoke potentiates the DNA-damaging effect of manmade mineral fibres. Am. J. Indust. Med. 16, 697-706. 

Slamenova D, Masterova I, Labaj J, et al. Cytotoxic and DNA-damaging effects of diterpenoid quinones from the roots of Salvia officinalis L. on colonic and hepatic human cells cultured in vitro. Basic Clin Pharmacol Toxicol 2004 94 282-290. 

Many sites of exposure to bile in the body are associated with the development of cancer, e.g. the oesophagus, gallbladder and bile duct, pancreas, small intestine and colon (reviewed in ref. 2). One explanation for increased cancer at these sites could be that bile acids stimulate carcinogenesis via DNA-damaging effects. This chapter provides an overview of research conducted in relation to establishing the genotoxic and carcinogenic effects of bile acids. 

Kandell and Bernstein published one of the earliest reports to suggest that bile acids also demonstrate DNA-damaging effects in eukaryotic cells. They showed that human foreskin fibroblasts underwent unscheduled DNA synthesis (indicating DNA repair), as measured by tritiated thymidine incorporation when cells were treated with increasing concentrations of sodium deoxycholate or chenodeoxycholate. Utilising mutant Chinese hamster ovary cells deficient in strand rejoining (EM9), the authors were able to demonstrate that the repair of deoxycholate-induced DNA damage was dependent on strand break repair capacity. 

Utilising a reversion assay in Salmonella enterica, Prieto et al reported an increased frequency of point mutations following bile-salt exposure. Mutations were predominantly nucleotide substitutions (GC to AT transitions) and -1 frameshift mutations.The frameshifts were dependent on SOS induction and linked to the activity of DinB polymerase (Pol IV). The authors proposed that the GC to AT transitions stimulated by bile, could have arisen from oxidative processes giving rise to oxidised cytosine residues. Consistent with this hypothesis, the authors demonstrated that strains of S. enterica-lacking enzymes required for base-excision repair (endonuclease III and exonuclease IV) and the removal of oxidised bases, demonstrated increased bile-acid sensitivity compared with competent strains. In another study using E. coli, resistance to the DNA-damaging effects of bile was associated with Dam-directed mismatch repair, a pathway also involved with the repair of oxidative DNA lesions. ... 

Jackson JH, Schraufstatter lU, Hyslop PA, et al. 1987. Role of oxidants in DNA damage Hydroxyl radical mediates the synergistic DNA damaging effects of asbestos and cigarette smoke. J Clin Invest 80 1090-1095. 

DNA-damaging effects of the alkaloids chelidonine and sanguinarine were detected in the comet assay, with sanguinarine being active at a lower concentration than chelidonine (Philchenkov et al. 2008). 

PhQchenkov, A., V. Kaminskyy, M. velevich, and R. Stoika. 2008. Apxjjjtogenic activity of two benzophenanthridine alkaloids from Chelidonium majus L. does not correlate with their DNA damaging effects. Toxicol. In Vitro 22 2) 2S7-295. 

In recent years, wine consumption was also linked to the development of tumors— but not in a positive way this time. Overconsumption of alcohol was proved to increase the risk of cancer in multiple studies. This is thought to be the consequence of the pro-oxidant and DNA damaging effects of alcohol consumption. But moderate drinking is not quite innocent, either it was shown to increase the risk of breast cancer (irrespectively of the source of alcohol, i.e. red wine included), especially among women with low body mass indexes. These results call for caution although the antioxidant effect of red wine is beyond doubt, it still cannot be recommended as a preventive tool against cancer. 

Liposome-encapsulated catalase (20 units) attenuated H202-induced (50juM for 30 min), but not amosite-induced (25/fg/cm ) DNA strand break formation in cultured type I like pulmonary epithelial cells (WI-26), suggesting that the DNA damaging effects of asbestos occur by both H2O2-dependent and H202-independent mechanisms (Kamp et al. 1997). 

Coogan TP, Bare RM, Waalkes MP (1992) Cadmium-induced DNA damage effects of zinc pretreatment. Toxicol Appl Pharmacol 113 227-233 Coogan TP, Bare RM, Bjornson EJ, Waalkes MP (1994) Enhanced metallothionein gene expression protects against cadmium genotoxicity in cultured rat liver cells. J Toxicol Environ Health (in press)... 

Li, Z., Zheng, Y., Cloutier, R, Sanche, L., 8c Wagner, J. R. (2008). Low energy electron induced DNA damage Effects of terminal phosphate and base moieties on the distribution of damage. Journal of the American Chemical Society, 130, 5612. 

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