The long-term objective of this proposed research is the formation of an in vitro cell culture model system for the study of cadmium-induced nephrotoxicity. The foundation of this model system is derived from the recently established cell culture of the human renal proximal tubule developed in this laboratory. In the last year, this culture system has been assessed with regard to the cellular responses which occur upon exposure to the heavy metal cadmium (Cd). Dose response curves demonstrated that these cells were very sensitive to low levels of Cd exposure and that these cells could become resistant to low levels of exposure and regain proliferative capacity. Both ultrastructural evaluation and electrophysiological analysis of these cells exposed to low Cd levels suggested an alteration in the structure and function of the cell membrane. Studies are proposed to examine: 1. alterations in proximal tubule cell transport and membrane structure that occur due to Cd exposure; 2. the localization of Cd within the cells when exposed both to CdC12 and the CdMT complex; 3. the metallothionein response of the cells when exposed to Cd; 4. if selective apical and basolateral membrane exposure to Cd alters the cellular toxicity of this compound; and, 5. whether or not similar alterations in proximal tubule cell membrane structure occur in in vivo models of Cd exposure. These studies should form a cell culture model system for the study of Cd-induced proximal tubule cell toxicity which compliments existing in vivo model systems.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
Application #
Study Section
Toxicology Subcommittee 2 (TOX)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Medical University of South Carolina
Schools of Medicine
United States
Zip Code
Bylander, J E; Li, S L; Sens, M A et al. (1994) Induction of metallothionein mRNA and protein following exposure of cultured human proximal tubule cells to cadmium. Toxicol Lett 71:111-22
Hazen-Martin, D J; Tarnowski, B I; Todd, J H et al. (1994) Serum-free culture and characterization of renal epithelial cells isolated from human fetal kidneys of varying gestational age. In Vitro Cell Dev Biol Anim 30A:356-65
Tarnowski, B I; Sens, D A; Nicholson, J H et al. (1993) Automatic quantitation of cell growth and determination of mitotic index using DAPI nuclear staining. Pediatr Pathol 13:249-65
Todd, J H; Sens, M A; Hazen-Martin, D J et al. (1993) Variation in the electrical properties of cultured human proximal tubule cells. In Vitro Cell Dev Biol Anim 29A:371-8
Hazen-Martin, D J; Todd, J H; Sens, M A et al. (1993) Electrical and freeze-fracture analysis of the effects of ionic cadmium on cell membranes of human proximal tubule cells. Environ Health Perspect 101:510-6
Todd, J H; Sens, D A; Sens, M A et al. (1992) In situ freeze-fracture of monolayer cell cultures grown on a permeable support. Microsc Res Tech 22:301-5