Effects on DNA Synthesis

DNA synthesis was strongly inhibited within an hour after removal of the drug, suggesting that an early (possibly immediate-early ) viral protein was involved (Ben-Porat et al., 1974). On the other hand, experiments with UV-inactivated HSV-1 and HSV-2 have shown that host DNA synthesis can be suppressed without detectable synthesis of viral proteins (Newton, 1969 Fenwick and Walker, 1978). 

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P. Pellack-Walker, J. K. Walker, H. H. Evans, J. L. Blumer, Relationship between the Oxidation Potential of Benzene Metabolites and Their Inhibitory Effect on DNA Synthesis in L5178YS Cells , Mol. Pharmacol. 1985, 28, 560 - 566. 

Mechanism of Action An antibacterial agent that inhibits bacterial protein, RNA synthesis. Less effective on DNA synthesis. Nasal Eradicates nasal colonization of MRSA. Therapeutic Effect Prevents bacterial growth and replication. Bacteriostatic. Pharmacokinetics Metabolized in skin to inactive metabolite. Transported to skin surface removed by normal skin desquamation. 

Wang C, Kurzer MS. Phytoestrogen concentration determines effects on DNA synthesis in human breast cancer cells. Nutr. Cancer 28, 236-247, 1997. 

Varrault A, Bockaert J, Waeber C. Activation of 5-HT1A receptors expressed in NIH-3T3 cells induces focus formation and potentiates EGF effect on DNA synthesis. Mol Biol Cell 1992 3 961-969. 

Norton, L.A. Shteyer, A. Rodan, G. A. Electromagnetic field effects on DNA synthesis in bone cells. American Electrochemical Society, 157th Meeting, St. Louis, Missouri,... 

Gangarosa, L. R, Park, N. H., and Hill, J. M. lontophoretic assistance of 5-iodo-2 -deoxyuridine penetration into neonatal mouse skin and effects on DNA synthesis (39689). Proc. Soc. Exp. Biol. Med. 154 439, 1977. 

The effect on DNA synthesis with Klenow fragment using C4 -alkyl (H, Me, Et and Pr) modified ODNs has been studied. When at the 3 -end of the primer, such modifications resulted in inhibition of chain extension. However, at positions -1- 2 to -4-4, the larger the alkyl group, the lower the efficiency for chain extension. In the template, strand inhibition of extension occurs at -l- 2 and + 4 positions even with the smaller alkyl chains. Thus these analogues have been... 

One of the biochemical adverse effects of nitric oxide is inactivation of vitamin B12, with subsequent potentiation of folate deficiency (19). This effect is mediated by irreversible oxidation of the cobalt residue in vitamin B12 to its Co++ and Co forms. This leads to a reduction in methionine synthetase activity, with downstream effects on DNA synthesis. Previous studies have identified five patients with unsuspected vitamin B12 deficiency who developed subacute combined degeneration of the spinal cord following inhalation anesthesia with nitrous oxide... 

The likely basis for this selective biochemical effect on DNA synthesis came from the observation that the inhibition of DNA synthesis was persistent and progressive with time after removal of the drug. It is now clear, particularly by comparison with analogous effects produced by direct reacting agents such as mustard gas, that both effects are consistent with the view that the primary chemical lesion is in the DNA of the cell, which is then inhibited as a template for DNA replication. 

Different lignans, including some known phytoestrogens, were evaluated for their effects on DNA synthesis in estrogen-dependent and independent human breast cancer cells. At 0.1-10 pM, enterolactone induced DNA synthesis by 150-235%, and at 20-90 pM it inhibited DNA synthesis by 50%. Inhibition of estrogen-dependent and independent breast cancer cells... 

Cemilton , a product obtained from rye pollen, is an effective agent in the treatment of prostatic inflammatory disease and benign prostatic hyperplasia [139]. In 1995, DIBOA was identified as a constituent of the water soluble pollen extract [66]. The purified active fraction of Cemilton showed dose-dependent effects on DNA-synthesis in epithelial cells. At low concentrations, DNA synthesis was stimulated, indicated by a 300% increase in radiolabelled thymidine incorporation. Concentrations larger than 1 pg/ml resulted in an inhibition up to 80% after 5 days of exposure. Fibroblast cells react in a similar way and prostate DU 145 cells showed the same inhibition after treatment with the active fraction as they do after exposure to synthetic DIBOA. From the studies is was clear, that DIBOA must be causative for the effects of Cemilton. Cell growth inhibition was thought to be due to the chelating properties of the compound [67]. As demonstrated MCF-7 breast cancer-and COS-7-cells were inhibited as well [140]. From the morphology of treated DU-145 cells the authors concluded DIBOA-induced cell death. 

Biochemical Connections What would be the effect on DNA synthesis if the telomerase enzyme were inactivated ... 

The 2, 3 -dideoxynucleosides can be used as reagents to inhibit DNA replication. These analogs must be converted to dideoxynucleoside triphosphates in order to have a measurable effect on DNA synthesis. When incorporated into a growing DNA chain, a single dideoxyribonucleoside residue can effectively block subsequent chain extension. 

The evidence that novobiocin exerts a specific and primary effect on DNA synthesis in E. coli was the subject of a recent report [33]. In all strains of E. coli employed in this study, DNA synthesis was inhibited earlier and to a greater extent than were other macromolecular syntheses. The antibiotic did not cause degradation of DNA its action was reversible, for when the... 

Recent findings show that the antibiotic has an immediate and pronounced effect on DNA synthesis and this may be of primary importance. It has also been shown that novobiocin interferes at an early stage with membrane integrity and, in view of the close association between membrane and chromosome in the bacterial cell, these findings have to be carefully considered. 

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