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Title: Model studies for the interaction of cis-platin with lead in bone
Author: Evetts, I. A.
Awarding Body: University College of Swansea
Current Institution: Swansea University
Date of Award: 1991
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A study carried out by the Swansea in vivo Analysis Research Group (SIVARG) showed evidence of Pb mobilisation to the kidney under the action of the drug cis-platin in four of ten cancer chemotherapy patients. This report was undertaken to ascertain the implications of this observation and provide a more detailed picture of the mobilisation sequence. Exchange studies on Pb-doped samples of the inorganic bone model hydroxyapatite at physiological temperatures and pH, provided evidence of a reaction between cis-platin and Pb (II) in the solid, the amount of Pb(II) released being equivalent to that contained in the surface layer(s). Kinetic analysis showed this reaction to be stoichiometric rather than purely catalytic, with maximum Pb(II) release corresponding to a 1:1 Pb(II)/Pt(II) ratio. The catalytic nature is shown to be a probable consequence of the basic structure of the hydroxyapatite surface. Analysis of the urine of chemotherapy patients undergoing cis-platin therapy by glow-discharge mass spectrometry (GDMS) confirmed of the effect, though its magnitude was less than predicted in the SIVARG study. None of the patients, however, had been occupationally exposed to the element. The analysis of trace elements in biological fluids is dominated by a variety of AAS techniques with various limits of detection and sensitivities. These studies represent a new application for GDMS and the performance and set-up of a home-built device is described. Pb(II) is shown to be released predominantly from the bone surface, appearing in the urine 6-9 hours after cis-platin excretion. This is reflected in some renal dysfunction. Effects are complicated by conditions of hypercalcaemia with malignancy. High Pb(II) exposure conditions were simulated in rats. Kidney dysfunction was seen to increase as a direct consequence of the introduction of cis-platin in 40% of these cases. This was associated with a higher number of Pb-specific intranuclear inclusions, shortage of red blood-cells, cellular necrosis and atrophic areas. Effects of Pb(II) were worsened by the existence of Pt(II) and vice-versa. Pb(II) release is independent on its availability, not solely Pb(II) content, the degree of bone turnover during the time of treatment and individual sensitivities and tolerance limits to the element.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available