Cellular activities kinetics

The reversibility of QM adducts also creates numerous challenges. For example, measuring the full burden of DNA alkylation by a QM can be obscured by the loss of its labile products during or before chemical identification can be completed. Results from a deoxynucleotide model system indicated that only a small fraction of the possible adducts could be measured after the interval required for analysis of DNA. Perhaps the kinetic products of QMs also contribute to the cellular activity of these intermediates although this has yet to be explored. QM equivalents can be envisioned to migrate from one reversible nucleophile such as the N1 of adenine in such cofactors as ATP to another until quenched by a compound such as glutathione that is present in cells as a defense against undesirable electrophiles. 

All the steps necessary for cellular transformation and cancer induction were demonstrated in cultured human skin fibroblasts inducible AHH activity, altered cellular proliferation kinetics, and DNA damage (Milo et al. 1978). Thus, humans are likely to be susceptible to tumor induction by PAHs by these mechanisms. 

Topologically defined kinetic analyses of cellular activities... 

Ionic concentration gradients across membranes serve a variety of functions in cellular activity such as maintainance of resting potential, transmission of nerve impulse, driving cotransport, and secretion or activation of enzymes, hormones and other substances. Thus, studies of the kinetics and mechanism of ion transport across membranes are essential for the understanding of many physiological processes. 

Direct quantitation of receptor concentrations and dmg—receptor interactions is possible by a variety of techniques, including fluorescence, nmr, and radioligand binding. The last is particularly versatile and has been appHed both to sophisticated receptor quantitation and to dmg screening and discovery protocols (50,51). The use of high specific activity, frequendy pH]- or p lj-labeled, dmgs bound to cmde or purified cellular materials, to whole cells, or to tissue shces, permits the determination not only of dmg—receptor saturation curves, but also of the receptor number, dmg affinity, and association and dissociation kinetics either direcdy or by competition. Complete theoretical and experimental details are available (50,51). 

The cellular automata approach to this problem would generally demand a second-order simulation, and this indeed can be done [5]. However, it is possible to simplify the problem and write it in terms of first-order kinetics. To do this, one notes that both the activation and the deactivation of A depend directly on the concentration [M] of the species M... 

In line with expectations of kinetic inertness for third-row transition metals, little interest has been vested in the development of osmium anticancer drugs, as ligand-exchange rates did not seem favorable on the timescale of cellular processes. Our work, however, shows that the kinetic lability of such complexes can be timed to such extent that anticancer activity comes within range. We have demonstrated how rational chemical design can thus be applied to osmium-arene complexes resulting in specific... 

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