The assessment of epidermal growth factor binding and protein kinase activity as biomarkers of 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity in rainbow trout

Miscellaneous · Tue Jan 01 00:00:00 EST 1991

OSTI ID:5145476

Newsted, J L

Halogenated aromatic hydrocarbons (HAHs) are a group of synthetic contaminants that includes polychlorinated-dibenzodioxins (PCDDs) and biphenyls (PCBs). Due to their toxicity, tendency to bioaccumulate in aquatic food chains, their relative persistence and widespread distribution, these HAHs are of particular concern to the health of aquatic species in the Great Lakes. Several studies have shown that in the Great lakes, salmon accumulate HAHs to concentrations that are sometimes sufficient to cause adverse effects in the reproduction, development and survival of the early life stages of lake trout. Although HAHs exist as complex environmental mixtures, many HAHs are approximate isostereomers and produce similar toxic symptoms in a variety of animals. In this study the author has examined the relationship between the binding of EGF and TCDD-induced lesions in the liver of rainbow trout. Characterization of EGF binding and the EGF-stimulated tyrosine kinase activity showed that rainbow trout have an EGF receptor-like protein that binds EGF in a specific and saturable manner and has a molecular weight similar to that seen in mammals. Upon binding, EGF elicited a kinase activity that autophosphorylated tyrosine residues on the receptor and exogenous polypeptide substrates. EGF-stimulated tyrosine kinase activity was significantly reduced by tyrosine kinase inhibitors. Reduction in the binding of EGF was time and dose dependent manner TCDD-exposed rainbow trout and RTH-149 cells. The reduction in binding was accompanied by an increase in protein kinase C and tyrosine kinase activities. The alteration in EGF-binding and protein kinase activities were specific for HAHs that could induce cytochrome P-450. Studies with a rainbow trout hepatoma cell line, RTH-149, showed that alterations in EGF binding and protein kinase activity were correlated to increases in cell proliferation and DNA synthesis.

• Research Organization: Michigan State Univ., East Lansing, MI (United States)
• OSTI ID: 5145476
• Resource Relation: Other Information: Thesis (Ph.D.)
• Country of Publication: United States
• Language: English

Related Subjects

54 ENVIRONMENTAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
DIOXIN
TOXICITY
GREAT LAKES
WATER POLLUTION
GROWTH FACTORS
BIOCHEMICAL REACTION KINETICS
PHOSPHOTRANSFERASES
ENZYME ACTIVITY
TROUT
SENSITIVITY
BIOLOGICAL MARKERS
CELL PROLIFERATION
DNA REPLICATION
DOSE-RESPONSE RELATIONSHIPS
ENZYME INHIBITORS
HEPATOMAS
LIVER
MOLECULAR WEIGHT
RECEPTORS
TUMOR CELLS
ANIMAL CELLS
ANIMALS
AQUATIC ORGANISMS
BODY
DIGESTIVE SYSTEM
DISEASES
ENZYMES
FISHES
GLANDS
HETEROCYCLIC COMPOUNDS
KINETICS
LAKES
MEMBRANE PROTEINS
MITOGENS
NEOPLASMS
NUCLEIC ACID REPLICATION
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PHOSPHORUS-GROUP TRANSFERASES
POLLUTION
PROTEINS
REACTION KINETICS
SURFACE WATERS
TRANSFERASES
VERTEBRATES
540320* - Environment
Aquatic- Chemicals Monitoring & Transport- (1990-)
560300 - Chemicals Metabolism & Toxicology