Reaction cellular distribution

Fig. 2 shows incorporation as function of temperature obtained from a crude homogenate of Sulfolobus solfataricus harvested in the late logarithmic growth phase (Fig.l, B). ADP-ribosyl transferase activity increased quickly from 15 C, showed a transient plateau from 30 C to 50°C and reaches a maximum value at 80 °C. To obtain information about cellular distribution of the ADP-ribosyl transferase activity, enzymatic activity was determined either on the soluble protein fraction (14) or on the nucleoprotein fraction obtained according to Searcy (15). The results showed a preferential association of the ADP-ribosyl transferase activity to the nucleoprotein fraction with a 45-fold increase of specific activity relative to cmde homogenate. Identification of the reaction product as ADP-ribose was... 

Model reactions on [AuCl(PEt3)] with GSH show chloride displacement but no phosphine displacement [40], and intracellular GSH binding to auranofin was also observed by NMR studies on red cells [14]. The presence of the phosphine, necessary for oral administration, may also dictate some of the biochemical differences between auranofin and the injectable gold complexes. The breakdown of auranofin eventually produces Et PO, a reaction interestingly mimicked by 2,3-dimercaptopropanol (or British Anti-Lewisite) in its reactions with gold—phosphine complexes [14]. The phosphine oxide has recently been detected in human serum [41], supporting the theory that, upon cellular distribution, loss of phosphine results in behavior similar to that of non-phosphine containing complexes. 

Snyder, R.M., Mirabelli, C. and Crooke, S.J. (1986) Cellular association, intracellular distribution, and efflux of auranofin via sequential ligand exchange reactions. Biochemical Pharmacology, 35, 923-932. 

The frequency distribution of the TMRP measurements shows for both levels of exposure a bi-modal histogram - in contrary to the log-normal distribution of the control values (Figure 7 ) The bimodal distribution could be due to a reaction at the cellular level indicating a critical number of hits, i.e. peak A is representing the cell population with a TMRP unaffected by low level alpha exposure, while peak B represents cells reacting to alpha hits. 

In contrast to many chemotherapeutic agents in cancer therapy, boron compounds for BNCT do not require a tumoricidal action in their own right. For their successful application in the therapy of patients, it is important to deliver, to the tumor, a radiation dose which is higher than the radiation dose to the surrounding tissue. The demonstration that this is actually achieved lies ultimately in the treatment of the tumor in question. Because of the short range of the particles produced in the 10B(n,a)7Li reaction, it is very important where, on a cellular and subcellular dimension, the neutron capture reaction takes place. Different methods for boron detection and quantification give different resolution of the boron distribution. It is instructive to compare these methods, both for their precision and lower detection limits, as well as for their ability to yield an image of the boron distribution in tissue (Table 2.2-1). 

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