Enzyme-catalysed toxicity
CYP-catalysed bioactivation and cell-specific toxicityThe CYP1 family and AhR-mediated toxicity
CYP-catalysed bioactivation and cell-specific toxicity
Principal investigator: Ingvar Brandt
The project is based on original observations that certain environmental contaminants can undergo cell-specific metabolic activation, form irreversibly bound adducts, and eventually induce localised degeneration or necrosis in the target cells.
In some of the studied cases, the lesion will be repaired. In other cases, secondary persistent lesions will develop, characterised by severe remodelling (metaplasia) of the tissue.
Identified targets of interest (and prototype chemicals) include:
- the adrenal cortex (3-methylsulphonyl-DDE)
- the olfactory system (2,6-dichlorophenyl methylsulphone)
- vascular endothelia (benzo(a)pyrene)
In this project we also examine mechanisms of placental transport and embryonic/foetal accumulation/binding of reproductive toxicants in normal and transgenic mice, e.g. TTR- and mdr 1-2 knockout mice.
Staff presently involved: Graduate student Vendela Asp, PhD Ulrika Bergström, PhD Jan Olsson, and professor Björn Brunström.
Recent doctoral theses: Veronica Lindström 2007, Alexandra Abrahamson 2007, Maria Jönsson 2004, Carina Carlsson 2003, Maria Johansson 2002, Örjan Lindhe 2001, Lizette Granberg 2001, Fariba Bahrami 2000.
The CYP1 family and AhR-mediated toxicity
Principal investigator: Maria Jönsson
This project is focused on the cytochrome P450 1 (CYP1) family in vertebrates, i.e., the CYP 1A, 1B, 1C, and 1D genes and enzymes. The goal is to find out more about their normal functions and possible involvement in pollutant toxicity. It is hypothesized that the multiple CYP1 enzymes play physiological roles during growth and development and that they are involved in aryl hydrocarbon receptor (AhR)-dependent toxicity.