Sage Journals: Discover world-class research

Abstract

The distribution of 3,4,3',4'-tetrachlorobiphenyl (TCB), its effects on serum and hepatic retinoid content, and liver morphology were investigated in adult female WAG/Rij rats. Animals received a single intraperitoneal injection of either a corn oil vehicle, 15 or 200 mg TCB/kg body weight and were killed at 1, 3, 7, and 14 days after treatment. One rat of the high-dose group that had received 200 mg TCB/kg containing 1.85 mCi of ³H-TCB was sacrificed at each sampling time. There was a significant increase in liver weight when expressed as a percentage of body weight in the high-dose group at day 3 (122% of controls), day 7 (116% of controls), and day 14 (110% of controls). There was a rapid rise in the amount of ³H-TCB present in the liver that peaked at day 7 followed by a rapid decline in the amount of radiolabeled material by day 14. Greater than 90% of the radiolabeled material in the liver was parent compound. TCB treatment induced a significant decrease in serum retinol content in the high-dose group at day 3 (39% of controls) and day 7 (46% of controls) following exposure. There was a significant decrease in hepatic retinol content in the high-dose group at day 3 (34% of controls), day 7 (25% of controls), and day 14 (42% of controls) following exposure. TCB treatment induced a significant decrease in hepatic retinyl palmitatc content in the high-dose group at day 7 (56% of controls) following exposure. Ultrastructural alterations in hepatocytes included the proliferation and vesiculation of endoplasmic reticulum, and mitochondrial enlargement with paracrystalline inclusions. There was an associated change in the number, size, and distribution of lipid droplets in hepatocytes and fat-storing cells following exposure. The results of this study indicate that TCB treatment induces a marked reduction in serum and hepatic retinoid content accompanied by morphologic changes in liver cell populations.

Keywords

Tetrachlorobiphenyl toxicity liver ultrastructurc vitamin A homeostasis

References

1. Bitman J , Cecil HC , and Harris SJ (1972). Biological effects of polychlorinated biphenyls in rats and quail. Environ. Health Perspect. 1: 145–149.

2. Birnie JH and Grayson J (1952). Observations on temperature distribution and liver blood flow in the rat. J. Physiol. 116: 189–201.

3. Brouwcr A , van den Berg KJ , and Kukler A (1985). Time and dose responses in retinoid concentrations in C57BL/Rij and DBA/2 mice induced by 3,4,3′,4′-tetrachlorobiphenyl. Toxicol. Appl. Pharmacol. 78: 180–189.

4. Brouwer A (1987). Interference of 3,4,3′,4′-tetra-chlorobiphenyl in vitamin A (retinoids) metabolism: Possible implications for toxicity and carcinogenicity of polyhalogenated aromatic hydrocarbons. Thesis, University of Leiden.

5. Brouwer A and van den Berg KJ (1986). Binding of a metabolite of 3,4,3′,4′-tetrachlorobiphenyl to transthyretin reduces serum vitamin A transport by inhibiting the formation of the protein complex carrying both retinol and thyroxin. Toxicol. Appl. Pharmacol. 87: 301–312.

6. Brouwer A , Blaner WS , Kukler A , and van den Berg KJ (1988). A study on the mechanism of interference of 3,4,3′,4′-tetrachlorobiphenyl with the plasma retinol-binding proteins in rodents. Chem. Biol. Interact. 68: 203–217.

7. Driskel WJ , Neese JW , Bryant CC , and Bashor MM (1982). Measurement of vitamin A and vitamin E in human serum by high performance liquid chromatography. J. Chromatogr. 231: 439–444.

8. Godfrey NK (1985). Comparing the means of several groups. N. Engl. J. Med. 313: 1450–1456.

9. Goodman DS (1984). Plasma retinol binding protein. In: The Retinoids, Vol. 2, MB Sporn , AB Roberts , and DS Goodman (eds). Academic Press, New York, pp. 41–88.

10.

10. Harrison EH , Smith JE , and Goodman DS (1979). Unusual properties of retinyl palmitate hydrolase activity in rat liver. J. Lipid Res. 20: 760–771.

11.

11. Hendriks HJF , Verhoofstad WAMM , Brouwer A , de Leeuw AM , and Knook DL (1985). Perisinusoidal fat storing cells are the main vitamin A storage sites in rat liver. Exp. Cell Res. 160: 138–149.

12.

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

13.

13. Jonsson HT , Walker EM , Greene WB , Hugson MD , and Hennigar GR (1981). Effects of prolonged exposure to dietary DDT and PCB on rat liver morphology. Arch. Environ. Contam. Toxicol. 10: 171–183.

14.

14. Leo MA and Lieber CS (1988). Hypervitaminosis A: A liver lovers lament. Hepatol 8: 412–417.

15.

15. Leo MA , Sato M , and Lieber CS (1983). Effect of vitamin A depletion on the liver of humans and rats. Gasteroenterology 84: 562–572.

16.

16. McConnell EE (1985). Comparative toxicity of PCBs and related compounds in various species of animals. Environ. Health Perspect. 60: 29–33.

17.

17. Nilsson A (1977). Effects of anti-microtubular agents and cyclohexamide on the metabolism of chylomicron cholesterol esters by hepatocyte suspensions. Biochem. J. 162: 367–377.

18.

18. Prystowsky JH , Smith JE , and Goodman DS (1981). Retinyl palmitate hydrolase activity in normal rat liver. J. Biol. Chem. 256: 4498–4503.

19.

19. Reggiani G and Bruppacher R (1985). Symptoms, signs and findings in humans exposed to PCBs and their derivatives. Environ. Health Pcrspect. 60: 225–232.

20.

20. Safe S (1980). Metabolism, uptake, storage and bioac-cumulation. In: Halogenated Biphenyls, Terphenyls, Naphthalenes, Dibenzodioxins and Related Products, RD Kimbrough (ed). Elsevier/North Holland, Amsterdam, pp. 81–88.

21.

21. Schecter A , Tiernan T , Schaffner F , Taylor M , Gitlitz G , van Ness GF , Garrett JH , and Wagel DJ (1985). Patient fat biopsies for chemical analysis and liver biopsies for ultrastructural characterization after exposure to polychlorinated dioxins, furans and PCBs. Environ. Health Perspect. 60: 241–254.

22.

22. Turner JN and Collins DN (1983). Liver morphology in guinea pigs administered either pyrolysis products of a polychlorinated biphenyl transformer fluid or 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol. Appl. Pharmacol. 67: 417–429.

23.

23. Turner JN and Collins DN (1984). Liver morphology in guinea pigs fed pyrolysis products of a polychlorinated biphenyl transformer fluid continuously for 90 days. Toxicol. Appl. Pharmacol. 73: 464–477.

24.

24. van Hooft JIM (1986). Survey of mouse and rat breeding colonies at REP Institutes. TNO (internal publication), pp. 15–16.

25.

25. van Putten LM , van Bekkum DW , and de Vries MJ (1970). A severe chronic intoxication in a monkey colony. In: Infection and Immunosuppression in Subhuman Primates, H Baldner and WIB Beveridge (eds). Munksgaard, Copenhagen, pp. 155–166.

26.

26. Wassermann M , Wassermann D , Cucos S , and Miller HJ (1979). World PCBs map: Storage and effects in man and his biologic environment in the 1970s. Ann. N.Y. Acad. Sci. 320: 69–124.

3,4,3',4'-Tetrachlorobiphenyl-Induced Effects in the Rat Liver. I. Serum and Hepatic Retinoid Reduction and Morphologic Changes

Abstract

Keywords

References