Toxicity of polychlorinated biphenyl with special reference to porphyrin metabolism
Oral administration of a commercial PCB mixture to chickens caused a hepatic-type porphyria characterized by hepatic accumulation and urinary excretion of uroporphyrin. To clarify the mechanism of the porphyrinogenic activity of these PCBs, the authors studied the structural requirement of synthetic PCB for porphyrinogenic activities by using the cultured chick embryo liver cells and examined the relationship between induction of delta-aminolevulinic acid (ALA) synthetase and inhibition of uroporphyrinogen decarboxylase. They established that the porphyrinogenic effect of PCBs exhibits a sharply defined structure-activity relationship in that only 3,4,3',4'-tetrachlorobiphenyl and 3,4,5,3',4',5'-hexachlorobiphenyl produced a marked accumulation of uroporphyrin. They also demonstrated that in ALA-supplemented cultures, these same compounds lead to accumulation of a large amount of uroporphyrin III, whereas with other PCBs, which were weak inducers of porphyrin synthesis, the accumulated porphyrin was mostly protoporphyrin. Kinetic studies of the sequential decarboxylation of uroporphyrinogen with purified uroporphyrinogen decarboxylase were performed. The 3,4,3',4'-tetrachlorobiphenyl and 3,4,5,3',4',5'-hexachlorobiphenyl strongly inhibit uroporphyrinogen decarboxylase directly at two steps. The results confirmed that porphyrinogenic PCBs primarily inhibit uroporphyrinogen decarboxylase, leading to a depletion of heme as a result of which synthesis of ALA synthetase increased.
- Research Organization:
- Kyoto Univ. (Japan)
- OSTI ID:
- 5414671
- Journal Information:
- Environ. Health Perspect.; (United States), Vol. 59
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CHLORINATED AROMATIC HYDROCARBONS
BIOLOGICAL EFFECTS
LIVER
BIOCHEMICAL REACTION KINETICS
PORPHYRINS
METABOLISM
AMINOLEVULINIC ACID
ANIMAL CELLS
CHICKENS
DECARBOXYLASES
ENZYME ACTIVITY
LIGASES
STRUCTURE-ACTIVITY RELATIONSHIPS
AMINO ACIDS
ANIMALS
AROMATICS
BIRDS
BODY
CARBON-CARBON LYASES
CARBOXY-LYASES
CARBOXYLIC ACIDS
DIGESTIVE SYSTEM
ENZYMES
FOWL
GLANDS
HALOGENATED AROMATIC HYDROCARBONS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
KINETICS
LYASES
ORGANIC ACIDS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
REACTION KINETICS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
560301 - Chemicals Metabolism & Toxicology- Cells- (-1987)