Damage to cellular DNA

A genotoxin can be defined as any substance that causes damage to cellular DNA. This may occur via alterations to the DNA structure, sequence or... 

H. Ohshima, Y. Yoshie, S. Auriol and I. Gilibert, Antioxidant and pro-oxidant actions of flavonoids effects on DNA damage induced by nitric oxide, per-oxynitrite and nitroxyl anion, Free Radic. Biol. Med., 25 (1998) 1057-1065. M.K. Johnson and G. Loo, Effects of egpigallocatechin gallate and quercetin on oxidative damage to cellular DNA, Mutat. Res., 459 (2000) 211-218. 

Cadet J, Douki T, Gasparutto D, Ravanat J-L. (2005) Radiation-induced damage to cellular DNA Measurement and biological role. Rad Rhys Chem 72 293-299. 

Singlet oxygen is a well known cytotoxic agent (Special Topic 6.23) and may react with guanine or other parts of cellular DNA. Since the determination of the UVA-mediated damage to cellular DNA is still a difficult analytical problem, laboratory experiments with DNA models have become the best means to reveal the mechanistic details of photooxygenation reactions. 

Ravanat, J.-L., Sauvaigo, S., Caillat, S., Martinez, G.R., Medeiros, M.H.G., Di Mascio, P., Favier, A., and Cadet, J. (2004) Singlet-oxygen-mediated damage to cellular DNA determined by the comet assay associated with DNA repair enzymes. Biol. Chem., 385, 7-20. 

Cadet, J., Douki, T., and Sage, E. (2005) Ultraviolet radiation-mediated damage to cellular DNA. Mutat. Res., 571, 3-17. 

As mentioned earlier, the transformation from normal cells to first-stage cells can result from damage to cellular DNA which is not repaired prior to mitosis (Barrett and Wiseman, 1987). A mutation could result from numerous mechanisms such as single strand brea)cs to DNA or the formation of DNA adducts. 

In mice orally administered 400 or 1000 mg/kg of a hydro-methanolic extract of rue daily for 30 days, damage to cellular DNA was observed in the comet assay at the 1000 mg/ kg dose. Damage was observed at day 30 but not at day 20 or earlier. In the chromosomal aberration test with animals... 

Kaneko, T. Tahara, S. Takabayashi, F. Suppression of hpid hydroperoxide-indnced oxidative damage to cellular DNA by esculetin. Biol. Pharm. Bull. 2003, 26, 840-844. 

Cadet J, Douki T, Badouard C, Favier A, Ravanat J (2007) Oxidatively generated damage to cellular DNA. In Evans MD, Cooke MS (eds) Oxidative damage to nucleic acids. Landes Bioscience Springer, Austin, pp 1-13... 

Von Sonntag [7] has estimated that the direct effects contribute about 40% to cellular DNA damage, while the effects of water radicals amount to about 60%. A paper by Krisch et al. [15] on the production of strand breaks in DNA initiated by HO radical attack has the direct effects contribution at 50%. 

Further sequelae to lipid peroxidation include inhibition of membrane-bound, phospholipid-dependent sodium-potassium ATPase and calcium ATPase with changes in the electrolyte milieu, especially calcium overloading of the cell with subsequent further cell damage and cell death as well as inhibition of adenylate cyclase. This results in loss of function in the mitochondria and microsomes. Damage to the DNA leads to enzyme defects or impaired enzyme synthesis, which triggers further metabolic changes. This also causes a cellular overload with calcium and subsequent activation of... 

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