Induced DNA damage

In addition to direct effects of chemical compounds on the fetus, metabolic disturbances in the mother, such as diabetes or hyperthermia, or deficiencies of calories or specific nutrients such as vitamin A, zinc, and folic acid may lead to teratogenesis. Compounds that inhibit placental functions may also induce malformations, e.g., by inhibiting placental circulation. For example, hydroxyurea disrupts the placental circulation and induces malformations. In addition, it also induces DNA damage. 

Leanderson, P. and Tagesson, C. (1992). Cigarette smoke-induced DNA damage in cultured human lung cells role of hydroxyl radicals and endonuclease activation. Chem. Biol. Interact. 81, 197—208. 

Ueda, N. and Shah, S.V. (1992). Endonuclease-induced DNA damage and cell death in oxidant injury to renal tubular epithelial cells. J. Clin. Invest. 90, 2593-2597. 

Shires, T.K. (1982). Iron-induced DNA damage and synthesis in isolated rat liver nuclei. Biochem. J. 205, 321-329. 

Chen, L. and Dixon, K., Analysis of repair and mutagenesis of chromium induced DNA damage in yeast mammalian cells and transgenic mice, Environmental, Health Perspective, 106, 1027-1032, 1998. 

Markwick PRL, Doltsinis NL, Schlitter J (2007) Probing irradiation induced DNA damage mechanisms using excited state Car-Parrinello molecular dynamics. J Chem Phys 126 045104... 

Note THF = tetrahydrofuran BHT = butylated hydroxytoluene, an antioxidant Camptothecin (CM) = causes inhibition of the DNA enzyme topoisomerase (Top 1) which induces DNA damage and apoptosis DHT = dihydrotestosterone PrEC = normal prostate stromal cells LNCaP, PC-3, DU-145 = neoplastic prostate epithelial cells (See Table 21.1). 

Figure 3 A general scheme for cellular response to platinum-induced DNA damage.

Reactive Oxygen Species as Mediators of Drug- and Xenobiotic-Induced DNA Damage... 

REACTIVE OXYGEN SPECIES AS MEDIATORS OF DRUG- AND XENOBIOTIC-INDUCED DNA DAMAGE... 

Salgo and Pryor [111] studied the effect of Trolox C (a water-soluble analog of vitamin E) on peroxynitrite-mediated DNA damage in rat thymocytes. They proposed that peroxynitrite mediated the formation of TBAR products, which caused the DNA-protein crosslinks. The latter were inhibited by the posttreatment of cells with Trolox. However, Trolox produced no effects on hydrogen peroxide- or bleomycin-induced DNA damage in human lymphocytes [108],... 

UV-irradiated cells. Using cell-free cytosolic keratinocyte extracts, Simon and colleagues26 confirmed the role of membrane oxidation in NF-kB activation. Particularly important aspects of the experimental design employed by Simon and colleagues was the use of keratinocytes versus cells derived from a cervical cancer patient, and the use of biologically relevant UVB (290 to 320 nm) radiation versus UVC (200 to 290 nm) radiation, which is filtered out by the atmospheric ozone layer and does not reach the earth s surface. Overall, these data indicate that the activation of cytokine transcription, a step essential for the induction of immune suppression, can occur independently of UV-induced DNA damage and suggest that membrane lipid oxidation can serve as a UV photoreceptor. 

Chaudhuri S, BhattacharyyaN, BhattacharjeeB. Hydrogen peroxide-induced DNA damages in vitro revealed by electron microscopy. J Electron Microsc 1992 41 57-59. 

To develop methods to identify individual or population susceptibility to environmental carcinogens, focusing on regulatory mechanisms for metabolism of carcinogens or repair mechanisms for carcinogen induced DNA damage between individuals or populations. 

Kootstra A (1994) Protection from UV-B-induced DNA damage by flavanoids. Plant Mol Biol 26 771-774... 

Ostling, O. and Johanson, K.J., Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells, Biochem. Biophys. Res. Commun., 123, 291,1984. 

Olive, P.L., Banath, J.P., and Durand, R.E., Heterogeneity in radiation-induced DNA damage and repair in tumor and normal cells measured using the "comet" assay, Radiat. Res., 122, 86, 1990. 

The sensitivity to ionizing radiation is maximal in those cells able to activate a co-ordinate program of cell death (apoptosis) primed by the radiation-induced oxidative stress. Albeit apoptosis is a nuclear event and radiation-induced DNA damage is probably the most relevant mechanism of initiation of apoptosis, the control of the execution phase (and sometime also the initiation) takes place at the mitochondrial level. Radioresistance occurs... 

---