Chemical carcinogenesis in feral fish: uptake, activation, and detoxication of organic xenobiotics
The high prevalance of liver neoplasms in English sole (Parophrys vetulus) and substantially lower prevalence of neoplasms in a closely related species, starry flounder (Platichthys stellatus) captured from industrialized waterways, provide a unique opportunity to compare biochemical processes involved in chemical carcinogenesis in feral fish species. Because levels of aromatic hydrocarbons (AHs) in urban sediments are correlated with prevalences of liver neoplasms in English sole, the authors have initiated detailed studies to evaluate the effects of endogenous and exogenous factors on uptake, activation and detoxication of carcinogenic AHs, such as benzo(a)pyrene (BaP), using spectroscopic, chromatographic, and radiometric techniques. The results obtained thus far show that sole readily takes up AHs associated with sediment from urban areas and that the presence of other xenobiotics, such as PCBs, in sediment increases tissue concentrations of BaP metabolites. Extensive metabolism of BaP occurred whether sole was exposed to this AH via sediment, per os, or intraperitoneally. Substantial modification of hepatic DNA occurred and persisted for a period of 2-4 weeks after a single exposure to BaP. The level of covalent binding of BaP intermediates to hepatic DNA was 10-fold higher in juvenile than adult sole and 90-fold higher in juvenile sole than in Sprague-Dawley rat, a species which is resistant to BaP-induced hepatocarcinogenesis. These results, along with the authors findings that hepatic GST activity in flounder was two times higher than in sole, demonstrate that microsomal metabolism of BaP does not accurately reflect the differences in the ability of these fish to form BaP-DNA adducts in vivo and also suggest that detoxication of reactive intermediates is an important factor in determining the levels of DNA modification by AHs and resulting toxic effects in feral fish.
- Research Organization:
- National Oceanic and Atmospheric Administration, Seattle, WA
- OSTI ID:
- 6516281
- Journal Information:
- Environ. Health Perspect.; (United States), Vol. 71
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
BENZOPYRENE
DETOXIFICATION
METABOLIC ACTIVATION
TISSUE DISTRIBUTION
UPTAKE
CHLORINATED AROMATIC HYDROCARBONS
LABELLED COMPOUNDS
BILE
CARBON 14 COMPOUNDS
CARCINOGENESIS
FISHES
FLUORESCENCE
LIQUID COLUMN CHROMATOGRAPHY
LIVER
METABOLITES
RATS
TRITIUM COMPOUNDS
XENOBIOTICS
ANIMALS
AQUATIC ORGANISMS
AROMATICS
BIOLOGICAL MATERIALS
BODY
BODY FLUIDS
CHROMATOGRAPHY
CONDENSED AROMATICS
DIGESTIVE SYSTEM
DISTRIBUTION
GLANDS
HALOGENATED AROMATIC HYDROCARBONS
HYDROCARBONS
LUMINESCENCE
MAMMALS
MATERIALS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANS
PATHOGENESIS
RODENTS
SEPARATION PROCESSES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550501 - Metabolism- Tracer Techniques