S-phase in response

To clarify the reason why different circadian schedules of 5-FU delivery have distinct cytotoxic effects, we used the cell cycle automaton model to determine the time evolution of the fraction of cells in S phase in response to different patterns of circadian drug administration, for a cell cycle variability of 15%. The results, shown in Fig. 10.5, correspond to the case considered in Fig. 10.4, namely, entrainment of a 22-h cell cycle by the circadian clock. The data for Fig. 10.5a clearly indicate why the circadian schedule with a peak at 4 a.m. is the least toxic. The reason is that the fraction of cells in S phase is then precisely in antiphase with the circadian profile of 5-FU. Since 5-FU only affects cells in the S phase, the circadian delivery of the anticancer drug in this case kills but a negligible amount of cells. 

Agarwal, M. K., Hastak, K., Jackson, M. W., Breit, S. N., Stark, G. R., Agarwal, M. L. (2006). Macrophage inhibitory cytokine 1 mediates a p53-dependent protective arrest in S phase in response to starvation for DNA precursors. Proceedings of the National Academy of Sciences of the United States of America, 103, 16278—16283. 

There are marked species differences in response to nongenotoxic carcinogens and the data available support the position that human and some animal species such as guinea pigs are nonresponsive to the adverse effects of PPs seen in rodents. Studies with cultured human hepatocytes show that there is no peroxisome proliferation or induction of S-phase in response to PPs. Follow up studies of patients receiving fibrate PP dmg therapy confirm a lack of adverse effects. In addition, there was no increased rate of cancer in workers exposed to DEHP. The lack of response provides clear evidence that humans are... 

While the simulations of figs. 5.40 and 5.41 show reasonable agreement with experimental observations, there is one set of experiments for which the model fails to yield satisfactory results. These experiments, carried out by Devreotes Steck (1979), pertain to the effect of increasing the level of extracellular cAMP from zero up to 10" M in four successive phases lasting 225 s each. In response to such sequential increments, the cells synthesize and excrete cAMP in four well-separated peaks of varying magnitude (fig. 5.42a). In these conditions, numeri-... 

K9TB Deregulated p53 pathway in lung,P53 response elements-breast, and prostate tumors E2F/pRb fusion protein MLP-controUed E3-ADP in E3 region Wild-type p53 activated p53 response element driven pRb-E2F fiision protein mediates inhibition of S-phase in normal cells 54... 

Materials for Electrooptic Modulation. The fundamental phenomenon of Pockel s effect is a phase change, A( ), of a light beam in response to a low frequency electric field of voltage, V. Relevant relationships for coUinear electrical and optical field propagation are as foUows (1 6) ... 

Malefyt R. Meng Q. Kay AB. Phipps S. Lee TH. Ying S Early production of thymic stromal lymphopoie-tin precedes infiltration of dendritic cells expressing its receptor in allergen-induced late phase cutaneous responses in atopic subjects. Allergy 2009 64 1014-1022. 

During the S phase, mammahan cells contain greater quantities of DNA polymerase than during the nonsynthetic phases of the cell cycle. Furthermore, those eiKymes responsible for formation of the substrates for DNA synthesis—ie, deoxyribonucleoside triphosphates—are also increased in activity, and their activity will diminish following the synthetic phase until the reappearance of the signal for renewed DNA... 

Within the potential range where Ru(bpy)3 remains in the aqueous phase, photocurrent responses are clearly observed with a slow rising time of the order of 10 s as shown in Fig. 14(a). According to the convention employed by these authors, positive currents correspond to the transfer of a negative charge from water to DCE. No photoresponses were observed in the absence of either the dye in the aqueous phase or TCNQ in DCE. Further analysis of the interfacial behavior of the product TCNQ revealed that the ion transfer occurred outside of the polarizable window [cf. Fig. 14(d)], confirming that these photoresponses are not affected by coupled ion-transfer processes. An earlier report also showed photoeffects for the photoreduction of the viologen under similar conditions [131]. 

---