The interactions of 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) and 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) in TCDD-induced porphyria

Thesis/Dissertation · Sun Jan 01 04:00:00 EST 1989

OSTI ID:5524522

Yao, Cheng Catsby

Halogenated aryl hydrocarbon(HAH)-induced porphyria is caused by alteration of porphyrin metabolism and results in the accumulation of hepatic and urinary porphyrins. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (75 {mu}/kg) caused significant increases of hepatic porphyrin levels in C57BL/6 male, female and ovariectomized female, and C57BL/10 male mice 3 weeks after treatment. In contrast, 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) was inactive at a dose of 750 {mu}mol/kg. Cotreatment with MCDF (750 {mu}mol/kg) and 2,3,7,8-TCDD (75 {mu}g/kg) resulted in partial antagonism of 2,3,7,8-TCDD-induced porphyrin accumulation in female but not in male mice. In female C57BL/6 mice, 2,3,7,8-TCDD-induced porphyria was accompanied by the induction of hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) activities and the inhibition of uroporphyrinogen decarboxylase (UROD) activity. MCDF (750 {mu}mol/kg) did not significantly affect these enzyme activities. In coadministration studies, MCDF partially antagonized 2,3,7,8-TCDD-induced hepatic porphyrin accumulation but did not affect the activities of hepatic AHH, EROD or UROD. These results demonstrate that the induction of the monooxygenase enzyme activities and the inhibition of UROD activity by 2,3,7,8-TCDD and the development of porphyria are not coordinately regulated in C57BL/6 female mice. In cultured chick embryo hepatocytes, 2,3,7,8-TCDD caused a significant increase in porphyrin levels and induced AHH and EROD activities. MCDF and Aroclor 1254 partially antagonized the 2,3,7,8-TCDD induced AHH and EROD activities but not the porphyrin accumulation.

• Research Organization: Texas A and M Univ., College Station, TX (USA)
• OSTI ID: 5524522
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
BIRDS
CARBOXYLIC ACIDS
CHICKENS
DIOXIN
DISEASES
EMBRYOS
ENZYME ACTIVITY
ENZYMES
FOWL
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROXYLASES
INHIBITION
LIVER CELLS
METABOLIC DISEASES
METABOLISM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
OXIDOREDUCTASES
PORPHYRINS
SOMATIC CELLS
VERTEBRATES