Genotoxicity cytotoxic activities

Secchiero P, Zerbinati C, di Iasio MG et al (2007) Synergistic cytotoxic activity of recombinant TRAIL plus the non-genotoxic activator of the p53 pathway Nutlin-3 in acute myeloid leukemia cells. Curr Drug Metab 8 395 103... 

Koparal, A.T., B.A. Tiiylii, and H. Turk. 2006. In vitro cytotoxic activities of (+)-usnic acid and (-)-usnic acid on V79, A549, and human l)m phocyte cells and their non-genotoxicity on human lymphocytes. Hat. Prod. Res. 20(14) 1300. 

Fig. 5.1 Phases of cancer progression. When normal cells or tissues are subjected to genotoxic, cytotoxic, or carcinogenic insult, they may undergo transformation in a nitric-oxide-dependent manner. This process is characterized by activation of signaling cascades that result in increased proliferation and inhibition of apoptosis, causing neoplastic evolution in the process, which is accompanied by various biophysical and biochemical changes. Once the tumor is established, the release of angiogenic mediators is stimulated, leading to increased blood vessel formation, accompanied with increased vascularization of the tumor. Finally, in the metastatic phase, the tumors develop migratory and invasive properties that facihtate dissemination of the tumor and metastasis to secondary sites...

Martelli A, Allavena A, Ghia M, et al Cytotoxic and genotoxic activity of 1,3-dichloropropene in cultured mammalian cells. Toxicol Appl Pharmacol 120 114—119, 1993... 

DNA damage in the presence of cytochrome P450s (CYPs) and Cu(II) in vitro or in cells [Yoshino et al., 2004 Ahsan et al., 1999]. At higher concentrations curcumin exhibited genotoxicity and cytotoxicity in different systems [Cao et al., 2007]. At last, in vivo intervention trials using typical antioxidants such as ascorbate or carotenes yielded mostly disappointing results in terms of protection against oxidation-related diseases, sometime even increased the incidences of diseases [Stevenson and Hurst, 2007 Dinkova-Kostova and Talalay, 2008]. Obviously, the direct antioxidant capacity of plant phenolic compounds cannot explain their cytoprotective activities. 

A dose-and duration-related decrease in splenic lymphocyte viability (as measured by H-TdR incorporation) and immune response (as measured by IgM secretion) was observed in the absence of S9 activation. Addition of S9 enhanced this effect after acute-duration exposure. However, there was very little formation of benzo[a]pyrene/DNA adducts at benzo[a]pyrene concentrations of 1-200 pmol in the splenic lymphocytes this lack of effect was accompanied by a very low level of benzo[a]pyrene metabolism to DNA-adducting metabolites. Benzo[a]pyrene/DNA adducts were measured in liver and lung however, in the in v/vo experiment. This led the authors to suggest that benzo[a]pyrene-induced immunotoxicity as expressed by splenic lymphocytes was the result of a cytotoxic effect that was mediated, in part, by a genotoxic mechanism involving the formation of benzo[a]pyrene/DNA adducts remote from the spleen and a direct cytotoxic effect not requiring activation of benzo[a]pyrene to the reactive intermediate. 

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