ABSTRACT
Interactions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and estradiol were studied in three strains of mice: CD-1 and C57B/6 (TCDD sensitive) and DBA/2 (TCDD resistant at lower doses). Immature females were injected with 0-200 ng/kg/day estradiol for 2 weeks, s.c. On days 7, 9, 11, and 13, mice received 10 micrograms TCDD/kg by gavage. Relative uterine weight increased in mice of all three strains treated with estradiol alone. Uterine imbibition was suppressed by TCDD treatment, although this effect was antagonized in a saturable manner by coadministration of estradiol. TCDD induced aryl hydrocarbon hydroxylase (AHH) in liver microsomes of treated mice independent of estradiol dose and strain of mice (the dose of TCDD used was high enough to cause AHH induction in the resistant DBA/2 mice). Treatment of CD-1 mice, but not other strains, with TCDD and estradiol resulted in a decrease in the electrophoretic band of hepatic microsomal proteins comigrating with cytochrome P-450a and epoxide hydrase.
Subject(s)
Dioxins/toxicity , Estradiol/pharmacology , Mice, Inbred Strains/physiology , Microsomes, Liver/enzymology , Polychlorinated Dibenzodioxins/toxicity , Uterus/drug effects , Age Factors , Animals , Aryl Hydrocarbon Hydroxylases/metabolism , Body Weight/drug effects , Cytochrome P-450 Enzyme System/metabolism , Drug Interactions , Female , Mice , Organ Size/drug effects , Uterus/anatomy & histologyABSTRACT
Bioavailability of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) from contaminated soils from Times Beach, Missouri and Newark, New Jersey, was examined using liver concentrations and toxicity in guinea pigs observed up to 60 days following a single oral administration, and induction of cytochrome P-450 in rats sacrificed 24 hours after a single oral dose as endpoints. Both soils are contaminated with several chlorinated dioxins and numerous other compounds. Times Beach soil resulted in greater TCDD concentration in liver and TCDD was considerably more bioavailable from Times Beach soil than from Newark soil. However, both soils induced cytochrome P-450 activity to approximately the same extent. Moreover, similar banding patterns of microsomal proteins were seen on polyacrylamide electrophoretic gels. The many other compounds present in the soils, particularly in Newark, may account for the similar protein bands and levels of cytochrome P-450 observed.
Subject(s)
Cytochrome P-450 Enzyme System/biosynthesis , Dioxins/pharmacokinetics , Polychlorinated Dibenzodioxins/pharmacokinetics , Soil Pollutants/analysis , Animals , Biological Availability , Enzyme Induction , Female , Guinea Pigs , Male , Microsomes, Liver/enzymology , Missouri , New Jersey , Rats , Rats, Inbred StrainsSubject(s)
2,4,5-Trichlorophenoxyacetic Acid/toxicity , Dioxins/toxicity , Reproduction/drug effects , Soil Pollutants/toxicity , 2,4,5-Trichlorophenoxyacetic Acid/analysis , Animals , Chemical Industry , Dioxins/analysis , Female , Male , Mice , Polychlorinated Dibenzodioxins/analysis , Polychlorinated Dibenzodioxins/toxicity , Pregnancy , Soil Pollutants/analysisABSTRACT
Weanling C57B/6 female mice treated with 6 micrograms/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 3 times a week for one month (total dose 72 micrograms/kg) were observed to have greatly reduced relative uterine weights and histopathological changes in the uterus. Weanling CD-1 female mice were then treated with estradiol (E2) subcutaneously daily for 2 weeks. Half the mice also received 10 micrograms/kg TCDD in corn oil: acetone (9:1) by gavage 4 times during the second week. Control mice received either no E2 or no TCDD. Mice were killed on day 15 and autopsied. Relative uterine weights increased with increasing E2 doses; however, TCDD decreased this effect of E2 markedly. Liver microsomes from these animals showed that cytochrome P1-450 and P3-450 and, aryl hydrocarbon hydroxylase (AHH) induction by TCDD were independent of E2 dosage. Epoxide hydrolase was induced in TCDD treated animals. Gels showed an E2 dose dependent decrease in a protein migrating near epoxide hydrolase and 'P-450a' in animals receiving both E2 and TCDD. These results suggest that: E2 may act at the TCDD receptor; the TCDD receptor may be related to the estrogen receptor; the anti-estrogenic effects of TCDD are possibly independent of the Ah locus and AHH induction, and in TCDD-treated mice a protein migrating near epoxide hydrolase and 'P-450a' may be controlled by estrogen levels.
Subject(s)
Cytochrome P-450 Enzyme System/biosynthesis , Dioxins/toxicity , Estradiol/pharmacology , Liver/drug effects , Polychlorinated Dibenzodioxins/toxicity , Uterus/drug effects , Animals , Aryl Hydrocarbon Hydroxylases/biosynthesis , Dose-Response Relationship, Drug , Epoxide Hydrolases/biosynthesis , Estrus/drug effects , Female , Liver/enzymology , Mice , Mice, Inbred Strains , Organ Size/drug effectsABSTRACT
Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) is a highly toxic contaminant produced in the manufacture of phenoxy herbicides. Despite its high TCDD content, soil from a contaminated area associated with a 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) manufacturing site in Newark, New Jersey, did not induce acute toxicity when administered to guinea pigs (the most sensitive species) by gavage. Analysis of liver samples demonstrated low bioavailability of TCDD from this soil. A comparative analysis of soils showed that Soxhlet extraction was necessary for the determination of TCDD on Newark soil, whereas solvent extraction was sufficient for soil from Times Beach, Missouri. The difference in the bioavailability of TCDD from these soils is correlated with TCDD extractability and may be related to the different compositions of the soils.
