Mitochondria perform functions which are central to the life of most eukaryotic cells. These organelles can be considered the ultimate energy power house of a living cell. The role of mitochondria in cancer phenotype remains a fertile area of research. Several carcinogens are known to enter the mitochondria, resulting in impaired functioning and altered structure. Aflatoxin BI (AFB1) a primary type I mycotoxin elaborated by Aspergillus flavus and Aspergillus parasiticus, is carcinogenic for a wide species range. The epoxide is capable of binding to nucleic acids and proteins, resulting in induced mutations, cellular toxicity, and eventually carcinogenesis. Approximately 250 000 deaths occur annually in both China and Africa due to patients presenting with Hepatocellular Carcinoma (HCC). The causative agents being AFB1-ingestion via contaminated foods and feeds, and the Hepatitis B Virus infection. The toxin has a multifaceted mode of attack, capable of being activated to a highly reactive and carcinogenic derivative, the AFB1-8,9-epoxide, via the cytochrome P450 enzyme system of the microsomes, endoplasmic reticulum and also the mitochondria. The epoxide is capable of binding to nucleic acids and proteins, resulting in the formation of covalent adducts. The repeated occurrence of gold labelled toxin within mitochondria from hepatomas of patients presenting with HCC suggested that these organelles were direct sites of toxin binding. Despite observations that mitochondria appear as direct and perhaps preferential targets for attack by AFB1, the actual in vivo immunolocalisation and characterisation of bound AFB1 within liver mitochondria has not been reported previously. In addition the role of AFB1-protein binding within mitochondria was investigated to determine the mode of action of the toxin, within the mitochondrial system. Liver sections from rats treated with a single lethal dose of AFB1, showed distinct ultrastructural abnormalities viz. large nuclei, increased heterochromatin, and swollen mitochondria. Immunocytochemistry revealed for the first time, the selective localisation of conjugated gold labelled toxin within the mitochondria. Toxin was found in the intracristal and peripheral spaces and frequently within the mitochondrial matrix. The mitochondria isolated from treated rats revealed significant alterations and damage to the mitochondrial membranes. The cristae were also markedly swollen with the associated clearing of the mitochondrial matrix. Western blot immunoassays revealed the presence of five AFB1-bound proteins (150kDa, 50kDa, 25kDa, 18kDa, 14kDa) in the inner mitochondrial fraction of isolated mitochondria. High pressure liquid chromatography also revealed that a significant proportion (84%) of an initial dose of toxin, was absorbed by mitochondrial protein. This study is the first to show the presence of specific mitochondrial proteins involved in toxin binding. In addition, the presence of toxin within the mitochondria and the specific binding to inner mitochondrial proteins suggest that the toxin specifically targets the electron transport chain and hence effects ATP production. This study conclusively indicates that mitochondria are direct targets for attack by AFB1 during experimental carcinogenesis. Mitochondria therefore play an important role in AFB1-mediated carcinogenesis. / Thesis (M.Med.Sc.)-University of Natal, Durban, 1998.

The objectives of the study were to measure the concentrations of albumin, transferrin, IgG and uric acid in 2nd trimester amniotic fluid (AF) and to establish if these concentrations were associated with infant birth outcomes. / Amniotic fluid samples (n=230) were collected from mothers undergoing routine amniocentesis (12-20 wk). Maternal characteristics like height, pre-pregnancy weight, age, smoking status, parity and infant gender, birth weight and gestational age were collected from questionnaires and obstetrical medical chart review. AF samples were analyzed by capillary zone electrophoresis (CZE). / The results showed that the 2nd trimester AF uric acid was a significant predictor of infant birth weight (grams) and transferrin was negatively associated with gestational age in term infants.

Graduation date: 1962

Thesis (Ph. D.)--University of Wyoming, 2005. / Title from PDF title page (viewed on Feb. 22, 2008). Includes bibliographical references (p. 110-118).

Thesis (Ph. D.)--Brigham Young University. Dept. of Chemistry and Biochemistry, 2005. / Includes bibliographical references.

Thesis (Ph. D.)--Washington State University, December 2007. / Includes bibliographical references.

Diss. (sammanfattning) Umeå : Univ., 2003. / Härtill 6 uppsatser.

Thesis (D. Sc.)--University of Adelaide, 1988. / Collection of previously published articles. Includes Allozyme electrophoresis / B.J. Richardson, P.R. Baverstock and M. Adams (1986). Includes bibliographical references.

Thesis (Ph. D.)--University of Delaware, 2007. / Principal faculty advisor: Murray V. Johnston, III, Dept. of Chemistry & Biochemistry. Includes bibliographical references.

Thesis (Ph. D.)--University of Adelaide, Dept. of Biochemistry, 1992. / Cover title: Novel approaches to protein purification and analysis: counter-current electrophoretic filtering: spectral enhancement. Spine title: Protein purification and analysis. Includes bibliographical references.