Skip to main content
Log in

Comparison between the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and six other compounds on the vitamin A storage, the UDP-glucuronosyltransferase and the aryl hydrocarbon hydroxylase activity in the rat liver

  • Original Investigations
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrabromodibenzo-p-dioxin (TBrDD), 5-chloro-2-(2,4-dichlorophenoxy)phenol(3-Cl-predioxin) 4,5,6-trichloro-2-(2,4-dichlorophenoxy)phenol (5-Cl-predioxin), toxaphene, 3-methylcholanthrene (3-MC) and phenobarbital (PB) on the vitamin A storage, UDP-glucuronosyltransferase (UDPGT) and aryl hydrocarbon hydroxylase (AHH) activities in the liver of Sprague-Dawley rats was investigated. Vitamin A was determined as retinol by high pressure liquid chromatography. UDPGT was measured with p-nitrophenol as an aglycone and AHH with 3,4-benzopyrene as a substrate. Both in TCDD- and toxaphene-treated animals a reduced body weight gain was recorded, but no other overt signs of toxicity were seen in this study. Both the concentration and the total amount of hepatic retinol was significantly reduced in TCDD-, 3-MC-, PB- and TBrDD-treated animals. These compounds were also those which gave the most significant enzyme induction as regards the UDPGT and AHH activities. However, the reduction of hepatic retinol caused by these compounds did not correlate with the enzyme activities studied. When compared on a molecular basis, TCDD and TBrDD were in the order of several magnitudes more potent as reducers of hepatic retinol and likewise as enzyme inducers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abels JC, Gorham AT, Eberlin SL, Halter R, Rhoads CP (1942) Hepatic vitamin A in the rat as affected by the administration of dibenzanthracene. J Exp Med 76: 143–161

    Google Scholar 

  • Aitio A (1973) Glucuronide synthesis in the rat and guinea pig lung. Xenobiotica 3: 13–22

    Google Scholar 

  • Aitio A, Vainio H (1976) UDP-glucuronosyltransferase and mixed function oxidase activity in microsomes prepared by differential centrifugation and calcium aggregation. Acta Pharmacol Toxicol 39: 555–561

    Google Scholar 

  • Allcroft R, Lewis G (1963) Groundnut toxicity in cattle: Experimental poisoning of calves and a report on clinical effects in older cattle. Vet Rec 75: 487–493

    Google Scholar 

  • Baumann CA, Foster EG, Lavik PS (1941) The effects of certain carcinogens on vitamin A in the liver. J Nutr 21: 431–444

    Google Scholar 

  • Blomstrand R, Löf A, Östling H (1977) Studies on the metabolic effects of long-term administration of ethanol and 4-methylpyrazole in the rat. Vitamin A depletion in the liver. Nutr Metab (Suppll) 21: 148–151

    Google Scholar 

  • Cecil HC, Harris SJ, Bitman J, Fries GF (1973) Polychlorinated biphenyl-induced decrease in liver vitamin A in Japanese quail and rats. Bull Environ Contam Toxicol 9: 179–185

    Google Scholar 

  • Davison KL, Cox JH (1976) Methoxychlor effects on hepatic storage of vitamin A in rats. Bull Environ Contam Toxicol 16: 145–148

    Google Scholar 

  • DePierre JW, Moron MS, Johannesen KAM, Ernster L (1975) A reliable, sensitive, and convenient radioactive assay for benzyrene monooxygenase. Anal Biochem 63: 470–484

    Google Scholar 

  • Haley FL, Samuelsen GS, Brooklyn MA (1943) Vitamin A and the detoxication of monobromobenzene. J Lab Clin Med 28: 1079–1082

    Google Scholar 

  • Hauswirth JW, Brizuela BS (1976) The differential effects of chemical carcinogens on vitamin A status and on microsomal drug metabolism in normal and vitamin A-deficient rats. Cancer Res 36: 1941–1946

    Google Scholar 

  • IARC (1982) Evaluation of the carcinogenic risk of chemicals to humans. Chemicals, industrial processes and industries associated with cancer in humans. IARC Monogr (Suppl, vol 1–29) 4: 238–243

    Google Scholar 

  • Innami S, Nakamura A, Nagayama S (1974) Polychlorobiphenyl toxicity and nutrition II. PCB toxicity and vitamin A (2). J Nutr Sci Vitaminol 20: 363–370

    Google Scholar 

  • Innami S, Nakamura A, Kato K, Miyazaki M, Nagayama S, Nishide E (1975) Polychlorinated biphenyls toxicity and nutrition IV. PCBs toxicity and vitamin A (3). Fukuoka Acta Med 66: 579–584

    Google Scholar 

  • Innami S, Nakamura A, Miyazaki M, Nagayama S, Nishide E (1976) Further studies on the reduction of vitamin A content in the livers of rats given polychlorinated biphenyls. J Nutr Sci Vitaminol 22: 409–418

    Google Scholar 

  • Isselbacher KJ (1956) Enzymatic mechanisms of hormone metabolism II. Mechanism of hormonal glucuronide formation. In: Pincus G (ed) Recent progress in hormone research. Academic Press, New York, pp 134–151

    Google Scholar 

  • Kamath SA, Narayan KA (1972) Interaction of Ca2+ with endoplasmic reticulum of rat liver: A standardized procedure for the isolation of rat liver microsomes. Anal Biochem 48: 53–61

    Google Scholar 

  • Kociba RJ, Keyes DG, Beyer JE, Carreon RM, Gehring PJ (1979) Long-term toxicologic studies of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in laboratory animals. Ann NY Acad Sci 320: 397–414

    Google Scholar 

  • Lee M, Harris K, Trowbridge H (1964) Effect of the level of dietary protein on the toxicity of dieldrin for the laboratory rat. J Nutr 84: 136–144

    Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193: 265–275

    Google Scholar 

  • Miller GL (1959) Protein determination for large numbers of samples. Anal Chem 31: 964

    Google Scholar 

  • NIH (1982a) Carcinogenesis bioassay of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Swiss-Webster mice (dermal study). National Toxicology Program, Technical Report Series No. 201

  • NIH (1982b) Carcinogenesis bioassay of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Osborne-Mendel rats and B6C3F1 mice (gavage study). National Toxicology Program, Technical Report Series No. 209

  • Phillips WEJ (1963) DDT and the metabolism of vitamin A and carotene in the rat. Can J Biochem Physiol 41: 1793–1802

    Google Scholar 

  • Phillips WEJ (1965) Effects of dieldrin on the metabolism of vitamin A and carotene in the rat. Can J Physiol Pharmacol 43: 649–656

    Google Scholar 

  • Pilot HC, Sirica AE (1980) The stages of initiation and promotion in hepatocarcinogenesis. Biochim Biophys Acta 605: 191–215

    Google Scholar 

  • Poland A, Glover E (1974) Comparison of 2,3,7,8-tetrachlorodibenzo-p-dioxin, a potent inducer of aryl hydrocarbon hydroxylase, with 3-methylcholanthrene. Mol Pharmacol 10: 349–359

    Google Scholar 

  • Poland A, Glover E, Kende AS (1976) Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol. J Biol Chem 251: 4936–4946

    Google Scholar 

  • Pollock GA, Kilgore WW (1978) Toxaphene. Res Rev 69: 87–140

    Google Scholar 

  • Sporn MB, Newton DL (1982) Retinoids and chemoprevention of cancer. In: Zedeck MS, Lipkin M (eds) Inhibition of tumor induction and development. Plenum Press, New York London, pp71–100

    Google Scholar 

  • Thiess AM, Frentzel-Beyme R, Link R (1982) Mortality study of persons exposed to dioxin in a trichlorophenol-process accident that occured in the BASF AG on November 17, 1953. Am J Industr Med 3: 179–189

    Google Scholar 

  • Thunberg T, Ahlborg UG, Johnsson H (1979) Vitamin A (retinol) status in the rat after a single oral dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Arch Toxicol 42: 265–274

    Google Scholar 

  • Thunberg T, Ahlborg UG, Håkansson H, Krantz C, Monier M (1980) Effect of 2,3,6,8-tetrachlorodibenzo-p-dioxin on the hepatic storage of retinol in rats with different dietary supplies of vitamin A (retinol). Arch Toxicol 45: 273–285

    Google Scholar 

  • Thunberg T, Håkansson H (1983) Vitamin A (retinol) status in the Gunn rat: the effect of 2,3,7,8-tetrachlorodibenzo-20-p-dioxin. Arch Toxicol 53: 225–233

    Google Scholar 

  • Vainio H (1973) Drug hydroxylation and glucuronidation in liver microsomes of phenobarbital-treated rats. Xenobiotica 3: 715–725

    Google Scholar 

  • Vainio H, Hietanen E (1974) Induction deficiency of the microsomal UDP-glucuronosyltransferase by 3-methylcholanthrene in Gunn rats. Biochim Biophys Acta 362: 92–99

    Google Scholar 

  • Van Miller JP, Lalich JJ, Allen JR (1977) Increased incidence of neoplasms in rats exposed to low levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Chemosphere 10: 625–632

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thunberg, T., Ahlborg, U.G. & Wahlström, B. Comparison between the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and six other compounds on the vitamin A storage, the UDP-glucuronosyltransferase and the aryl hydrocarbon hydroxylase activity in the rat liver. Arch Toxicol 55, 16–19 (1984). https://doi.org/10.1007/BF00316580

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00316580

Key words

Navigation