Invention:
A novel human albumin transgenic mouse model was developed which can be used to establish human protein biomarkers of exposure to hazardous xenobiotics for human risk assessment via animal studies. This can provide a unique in vivo tool for the assessment of risks of toxicity associated with human exposure to environmentally hazardous chemicals and therapeutic drugs, using human albumin as a protein target. The researchers developed an alternative approach to the measurement of DNA adducts for assessing human exposure to hazardous chemicals through biomonitoring of protein-carcinogen adducts. Unlike DNA adducts, carcinogen-protein adducts do not undergo repair and are expected to have serum stabilities similar to that of the unmodified protein, expecting albumin adducts to accumulate during chronic exposure to genotoxicants.
Publication available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868631/.
Background:
Albumin is critical in maintaining the colloid osmotic pressure and transporting hormones, fatty acids, and many xenobiotic compounds including therapeutic drugs, environmental pollutants, and chemical carcinogens. There is a critical need to establish animal models that express human proteins for mechanistic studies with xenobiotics and to facilitate the development and validation of analytical methods to measure protein adduct biomarkers prior to studies in humans. Transgenic mouse models with a systemic expression of human albumin have not yet been reported and this invention provides this.
Applications:
- Assess human exposure to hazardous chemicals
- Biomonitoring of protein-carcinogen adducts
Advantages:
- Systemic expression of human albumin
- Accumulation of adducts during chronic exposure
