Call number: LD2668 .T4 1934 W61

Seven prospective biological indicators of systemic toxicity were examined at time points ranging from 15 minutes to 24 hours using male Sprague-Dawley rats, B6C3F1 mice, Golden-Syrian hamsters and Hartley guinea pigs following intraperitoneal dosing with 0.1 mg/kg and 1.0 mg/kg sodium arsenite. Rats and mice were also dosed with 1.0 mg/kg sodium arsenate. Pyruvate dehydrogenase (PDH) activity was significantly depressed at early time points in mice, hamsters and guinea pigs and at later time points in rats dosed with arsenic (III). Rats and mice dosed with arsenic (V) also exhibited PDH depression at early time points. Uroporphyrin and coproporphyrin excretion was elevated in mice following arsenic (III) dosing. Coproporphyrin excretion was elevated in rats following arsenic (V) dosing. Blood glucose, creatinine, urea nitrogen and creatinine were unchanged by arsenic dosing. Based upon the amount and types of biological responses observed, the mouse appears to be the most sensitive animal model for the further study of arsenic toxicity.

published_or_final_version / abstract / Medicine / Master / Master of Philosophy

Thesis (Ph. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

Lymphomas are malignant diseases involving the lymphatic system. Arsenic trioxide (As2O3) is a current therapeutic agent for acute promyelocytic leukaemia (APL).APL cells are sensitive to As2O3, with As2O3directly targeting the PML-RARA protein that plays an important role in the oncogenesis of APL. In order to discover the potential of As2O3as a treatment of lymphoma, understanding of the molecular mechanism of As2O3in human lymphoma cells is essential. In this thesis, we showed that the MYC gene is a therapeutic target for As2O3in B-cell lymphomas and the CCND1 (cyclin D1) gene is another therapeutic target for As2O3in mantle cell lymphoma (MCL), a subtype of non-Hodgkin lymphoma (NHL). Both real-time RT-PCR and immunoblotting analysis showed that the expression levels of MYC in all B-cell lymphoma cell lines were down-regulated at both mRNA and protein level after As2O3treatment. The expression levels of MYC were also found to positively correlate with the arsenic sensitivity as measured by MTT assay. Hence, the higher the level of MYC expression, the higher the arsenic sensitivity of human B-cell lymphoma cell lines. Besides, the change of downstream genes after modulation of MYC expression level by As2O3 treatment was investigated. The expression level of CDKN1A and CDKN1B was increased after As2O3 treatment. Interestingly, the growth rate of MYC over-expressing lymphoma cell lines decreased significantly after As2O3treatment, while there was no significant decrease in colony formation assay in lymphoma cells without MYC over-expression. Immunoblotting analysis showed that As2O3could degrade the cyclin D1 protein in mantle cell lymphoma cell lines in a dose-dependent manner. Real-time RT-PCR analysis also showed that the mRNA level of CCND1gene was decreased after As2O3treatment. We also demonstrated that As2O3-induced cyclin D1 protein degradation was related to the proteasome pathway. The growth rate of MCL cell line decreased significantly after As2O3treatmentby using colony formation assay. Human water channel protein, aquaporin 9 (AQP9) has been demonstrated to facilitate the arsenic uptake in human leukaemia cells. In this thesis, we showed that the expression levels of AQP9were found to positively correlate with the arsenic sensitivity as measured by MTT assay in B-cell lymphoma cells. We also demonstrated that dexamethasone could up-regulate AQP9expressions at both mRNA and protein levels in human B-cell lymphoma cell lines. These results not only suggest that As2O3is a potential therapy for B-cell lymphomas, especially for those MYC-over-expressed B-cell lymphomas and MCL, but also indicate that MYC may act as a biomarker for predicting the clinical behaviour of B-cell lymphoma patients to the As2O3treatment.Moreover, dexamethasone pre-treatment may enhance the therapeutic effect of As2O3by up-regulating AQP9expression in B-cell lymphomas. / published_or_final_version / Medicine / Master / Master of Philosophy

Arsenic contamination of groundwater has been reported in over 20 countries worldwide where tens of millions of people are being exposed to excessive levels of arsenic in their drinking water, especially in countries of the Asian region, Bangladesh in particular. This study focusses on analytical techniques currently used for the estimation and speciation of arsenic in aqueous phase (soil and water) and in plant tissues; the uptake of arsenic by two commonly used vegetable crops (amaranth and silverbeet) using solution culture and pot culture studies; speciation-toxicity relationship of arsenic to plants; the nature of arsenic species in plant tissue and Bangladesh groundwater samples; and the effect of iron (Fe) on arsenic (As) uptake by plants and animals. / Thesis (PhD)--University of South Australia, 2006.

Arsenic contamination of groundwater has been reported in over 20 countries worldwide where tens of millions of people are being exposed to excessive levels of arsenic in their drinking water, especially in countries of the Asian region, Bangladesh in particular. This study focusses on analytical techniques currently used for the estimation and speciation of arsenic in aqueous phase (soil and water) and in plant tissues; the uptake of arsenic by two commonly used vegetable crops (amaranth and silverbeet) using solution culture and pot culture studies; speciation-toxicity relationship of arsenic to plants; the nature of arsenic species in plant tissue and Bangladesh groundwater samples; and the effect of iron (Fe) on arsenic (As) uptake by plants and animals. / Thesis (PhD)--University of South Australia, 2006.

Thesis (M.S.)--University of North Carolina Wilmington, 2007. / Includes bibliographical references.

Thesis (M. Phil.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 101-108) Also available in print.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1934. / Typescript. With this is bound: The arsenamides : compounds containing the As-N linkage / by G.O. Doak. Reprinted from Journal of the American Pharmaceutical Association, vol. XXIV, no. 6 (June 1935), p. [453]-457. Includes bibliographical references (leaves 76-81).