Induction of DNA fragmentation

Robbiano, L., Carrozinno, R., Porta Pugjia, C., Corbu, C., Brambilla, G., 1999. Correlation between induction of DNA fragmentation and micronuclei formation in kidney cells from rats and humans and tissue-specific carcinogenic activity. Toxicol. Appl. Pharmacol. 161, 153—159. Rossner, P., Boffetta, P., Ceppi, M., Bonassi, S., Smerhovsky, Z., Landa, K., et al., 2005. Chromosomal aberrations in lymphocytes of healthy subjects and risk of cancer. Environ. Health Perspect. 113, 517—520. 

After the discovery that low energy (3-20 eV) electrons induced single- and double-strand breaks in plasmid DNA (Boudaiffa et al. 2000), a number of theoretical studies have attempted to elucidate the mechanism of LEE induction of DNA strand breaks. As the calculation of the entire DNA molecule at the ab initio or DFT levels is currently prohibitive fragments of DNA structure usually including the base, sugar and phosphate attached at 3 - and 5 - ends of the sugar ring have been treated. 

Figure 4. Induction of DMA fragmentation in HL-60 cells. (A) Cells were treated with increasing concentrations of tested compounds for 18 h. Abbreviations carnosic acid (CA), carnosol (CL), ursolic acid (UA). (B) Cells were treated with 30 pM carnosic acid, 20 pM carnosol, or 40 pM ursolic acidfor different time periods. DNA fragments were separated by electrophoresis in 2% agarose...

Ohta, H., Sweeney, E.A., Masamune, A., Yatomi, Y., Hakomori, S-I. and Igarashi, Y., 1995, Induction of apoptosis by sphingosine in human leukemic HL-60 cells a possible endogenous modulator of apoptotic DNA fragmentation occurring during photbol ester-induced differentiation. Cancer Res. 55 691-697. 

Figure 19.5 Visualization of DNA damage induction in cultured human keratinocytes by photo-activated lomefloxacin using the comet assay. The presence of DNA breaks (induced either by ROS or by excision of DNA lesions) leads to fragmentation and electrophoretic migration to produce the comet tails, whereas bulky genomic DNA remains in the comets heads.

DNA single-strand breaks and fragmentations were observed in human lymphocytes and respiratory tract epithelial cells and in cultures of transformed human cells. Hydrogen peroxide induced unscheduled DNA synthesis and chromosomal aberrations in human fibroblast cells in vitro. It induced sister chromatid exchanges or chromosomal aberrations in human lymphocyte cultures and gave inconclusive results for induction of aneuploidy. 

Jarvis, W.D., Turner, A.J., Povirk, L.F., Traylor, R.S., and Grant, S., Induction of apoptotic DNA fragmentation and cell death in HL-60 human promyelocytic leukemia cells by pharmacological inhibitors of protein kinase C, Cancer Res., 54, 1707, 1994. 

On the other hand, there is strong evidence that the effects of flavonoids on cultured cells are not merely toxic but via induction of apoptosis or inhibition of proliferation. Thus signs of apoptosis, such as induction of caspase-3, fragmentation of DNA and chromatin condensation, are frequently detected upon cell exposure to flavonoids [213, 217-221]. In addition, the effects of flavonoids are generally reversible upon removal or addition of serum [222-224]. 

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