Genotoxic damage

Lu Y, Zhou WZ, Chang Z, Chen W-X and Li L. 2004. Procyanidins from grape seeds protect against phorbol ester-induced oxidative cellular and genotoxic damage. Acta Pharmacol Sin 25(8) 1083-1089. 

Tobi SE, Gilbert M, Paul N and McMillan TJ. 2002. The green tea polyphenol, epigallocatechin-3-gallate, protects against the oxidative cellular and genotoxic damage of UVA radiation. Int J Cancer 102(5) 439-444. 

Numerous test methods are available for assessing the genotoxic potential of substances. There are essentially three main categories of genotoxic damage that can be caused by a substance ... 

There are specific assays available to detect each of these types of genotoxic damage, and a battery of tests is often used to determine if a substance causes any or all of these 3 types of damage. An overview of which assays can be used to detect a given type of genotoxic effect is shown in the following table. 

Other evidence of genotoxicity induced by benzene includes inhibition of DNA synthesis in certain cell types, although inhibition of DNA synthesis is not always indicative of genotoxic damage. Acute 4-hour inhalation exposure of female ICR mice to 2,000 ppm benzene produced a 15% inhibition of DNA synthesis in bone marrow cells, and exposure to 3,000 ppm inhibited DNA synthesis by 33% (Lee et al. 1988). Delayed cell cycle in mouse bone marrow and DNA adducts with benzene metabolites in mouse and rat hemoglobin or rat liver cells were also evidence of benzene inhalation exposure (Lutz and Schlatter 1977 Sabourin et al. 1990 Tice et al. 1980, 1982). Other genotoxicity studies are discussed in Section 2.5. 

Additionally, several misfolded and/or mutated cellular proteins like protease resistance Prion (PrP ") (Prion disease). Parkin (Parkinson disease), Huntington (Huntington s disease), and amyloid-p (Alzheimer s disease) also cause neurodegeneration. Other intrinsic inducers include intracellular changes like, genotoxic damage, misbalance of intracellular Ca and anoikis. 

Salagovic, J., Gilles, J., Verschaeve, L. and Kalina, I. (1996) The comet assay for the detection of genotoxic damage in the earthworms a promising tool for assessing the biological hazards of polluted sites. Folia Biol., 42, 17-21. 

A possible but not yet fully proven carcinogenity of hardmetal dust could result from a synergism between the activated oxygen species (genotoxicity—damage to DNA) and the already proven repair inhibition by Co " ". 

VI. The options for a standard battery of genotoxicity tests are expanded by the possibility to choose to conduct an in vivo test with investigation of genotoxic damage in two tissues instead of conducting an in vitro test with mammalian cells followed by an in vivo test. 

The present theory of chemical carcinogenesis indicates that even the lowest dosc will produce some genotoxic damage irrespective if the observation or non-observation of tumour formation in finite expeiuneixtal conchtioQs (H chler 1991 15 quoted in Hanson... 

High sensitivity of this system to genotoxic damage allows selection of chemicals that have no or a negligible impact on plant genome integrity (Kovalchuk et al. 2001). Therefore, this test system makes it possible to develop clean transformation techniques in contrast to those that usually result in extensive DNA damage (Kohler et al. 1989, Leskov et al. 2001). 

Siddique, Y.H., G. Ara, T. Beg, et al. 2008. Antigenotoxic role of Centella asiatica L. extract against cyproterone acetate induced genotoxic damage in cultured human lymphocytes. Toxicol. In Vitro 22 iy.l0-7. 

---