Rapid toxicity testing based on mitochondrial respiratory activity
- Environmental Protection Agency, Ann Arbor, MI (USA)
- Univ. of Michigan, Ann Arbor (USA)
- Eastern Michigan Univ., Ypsilanti (USA)
The need exists for rapid and inexpensive methods to determine the health effects of environmental contaminants on biological systems. One of the current research approaches for assessing cytotoxicity is to monitor the respiratory activity of the mitochondrion, a sensitive, nonspecific subcellular target site. Detected changes in mitochondrial function after the addition of a test chemical could be correlated to toxic effects. Mitochondrial respiration can be characterized by three indices: state 3 and state 4 respiratory rates, and the respiratory control ratio (RCR). State 4, the idle or resting state, results when coupled mitochondrial respire in a medium containing inorganic phosphate and a Kreb's cycle substrate in the absence of a phosphate acceptor such as adenosine diphosphate (ADP). In the presence of ADP the respiration rate increases to a maximum (state 3), accompanied by phosphorylation of ADP to adenosine triphosphate (ATP). The ratio of state 3 to state 4, or RCR, indicates how tightly the oxidative phosphorylation process is coupled. The synthesis of ATP by mitochondria is influenced by a number of compounds, most of which are either uncouplers or inhibitors.
- OSTI ID:
- 6614555
- Journal Information:
- Bulletin of Environmental Contamination and Toxicology; (USA), Vol. 44:5; ISSN 0007-4861
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
MITOCHONDRIA
BIOCHEMISTRY
POLLUTANTS
BIOASSAY
ATP
ELECTRON TRANSFER
ENZYME INHIBITORS
KREBS CYCLE
LIVER
RATS
RESPIRATION
ANIMALS
BODY
CELL CONSTITUENTS
CHEMISTRY
DIGESTIVE SYSTEM
GLANDS
MAMMALS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology