Toxicity of polychlorinated biphenyl with special reference to porphyrin metabolism

Journal Article · Fri Feb 01 04:00:00 EST 1985 · Environ. Health Perspect.; (United States)

DOI:https://doi.org/10.2307/3429886· OSTI ID:5414671

Sano, S; Kawanishi, S; Seki, Y

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), Journal Name: Environ. Health Perspect.; (United States) Vol. 59; ISSN EVHPA
• Country of Publication: United States
• Language: English

Related Subjects

560301 -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINO ACIDS
AMINOLEVULINIC ACID
ANIMAL CELLS
ANIMALS
AROMATICS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIRDS
BODY
CARBON-CARBON LYASES
CARBOXY-LYASES
CARBOXYLIC ACIDS
CHICKENS
CHLORINATED AROMATIC HYDROCARBONS
DECARBOXYLASES
DIGESTIVE SYSTEM
ENZYME ACTIVITY
ENZYMES
FOWL
GLANDS
HALOGENATED AROMATIC HYDROCARBONS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
KINETICS
LIGASES
LIVER
LYASES
METABOLISM
ORGANIC ACIDS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PORPHYRINS
REACTION KINETICS
STRUCTURE-ACTIVITY RELATIONSHIPS
VERTEBRATES