Abstract
Our studies have evaluated biochemical changes in placentae from humans exposed to rice oil contaminated with polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) in Taiwan. Placentae were obtained from nonsmoking women 4 to 5 years after the exposure had occurred. The exposed individuals ingested approximately 1 to 3 g PCBs and 5 mg PCDFs, and many exhibited symptoms characteristic of PCB poisoning. This disease was termed "Yu-Cheng" in Chinese. Based on data from experimental animal models, we examined a number of parameters in placentae from control and exposed women, including arylhydrocarbon hydroxylase (AHH) activity, cytochrome P-450 isozymes, epidermal growth factor (EGF) receptor binding properties and actions, and Ah receptor. We also quantified concentrations of various PCB and PCDF congeners known to be present in the contaminated rice oil. Our results revealed a dramatic elevation in placental AHH activity in samples from PCB/PCDF-exposed women. This increase in enzyme activity was associated with a parallel increase in placental microsomal protein immunochemically related to cytochrome P-450 form 6 [derived from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced rabbit lung]. No other cytochrome P-450 isozyme was detected in placental preparations, and the form 6 homolog was found only in placentae from exposed women. EGF receptor-mediated autophosphorylation capacity was significantly diminished in PCB/PCDF placentae, but this effect was not associated with changes in plasma membrane EGF receptor binding properties (Kd and Bmax). The EGF receptor autophosphorylation effect correlated well with the decrease in birthweight observed in offspring of exposed women, suggesting that this biochemical event might provide a good marker of effect for the toxic halogenated aromatics.
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Selected References
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- Bandiera S., Sawyer T., Romkes M., Zmudzka B., Safe L., Mason G., Keys B., Safe S. Polychlorinated dibenzofurans (PCDFs): effects of structure on binding to the 2,3,7,8-TCDD cytosolic receptor protein, AHH induction and toxicity. Toxicology. 1984 Aug;32(2):131–144. doi: 10.1016/0300-483x(84)90132-x. [DOI] [PubMed] [Google Scholar]
- Carpenter G. The biochemistry and physiology of the receptor-kinase for epidermal growth factor. Mol Cell Endocrinol. 1983 Jul;31(1):1–19. doi: 10.1016/0303-7207(83)90027-8. [DOI] [PubMed] [Google Scholar]
- Chen P. H., Chang K. T., Lu Y. D. Polychlorinated biphenyls and polychlorinated dibenzofurans in the toxic rice-bran oil that caused PCB poisoning in Taichung. Bull Environ Contam Toxicol. 1981 Apr;26(4):489–495. doi: 10.1007/BF01622125. [DOI] [PubMed] [Google Scholar]
- Chen P. H., Wong C. K., Rappe C., Nygren M. Polychlorinated biphenyls, dibenzofurans and quaterphenyls in toxic rice-bran oil and in the blood and tissues of patients with PCB poisoning (Yu-Cheng) in Taiwan. Environ Health Perspect. 1985 Feb;59:59–65. doi: 10.1289/ehp.59-1568079. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chinkers M., Garbers D. L. Suppression of protein tyrosine kinase activity of the epidermal growth factor receptor by epidermal growth factor. J Biol Chem. 1986 Jun 25;261(18):8295–8297. [PubMed] [Google Scholar]
- Fujino T., Gottlieb K., Manchester D. K., Park S. S., West D., Gurtoo H. L., Tarone R. E., Gelboin H. V. Monoclonal antibody phenotyping of interindividual differences in cytochrome P-450-dependent reactions of single and twin human placenta. Cancer Res. 1984 Sep;44(9):3916–3923. [PubMed] [Google Scholar]
- Gasiewicz T. A., Rucci G. Cytosolic receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin. Evidence for a homologous nature among various mammalian species. Mol Pharmacol. 1984 Jul;26(1):90–98. [PubMed] [Google Scholar]
- Hsu S. T., Ma C. I., Hsu S. K., Wu S. S., Hsu N. H., Yeh C. C. Discovery and epidemiology of PCB poisoning in Taiwan. Am J Ind Med. 1984;5(1-2):71–79. [PubMed] [Google Scholar]
- Hudson L. G., Toscano W. A., Jr, Greenlee W. F. Regulation of epidermal growth factor binding in a human keratinocyte cell line by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Appl Pharmacol. 1985 Feb;77(2):251–259. doi: 10.1016/0041-008x(85)90324-2. [DOI] [PubMed] [Google Scholar]
- Johnson E. F., Muller-Eberhard U. Multiple forms of cytochrome P-450: resolution and purification of rabbit liver aryl hydrocarbon hydroxylase. Biochem Biophys Res Commun. 1977 Jun 6;76(3):644–651. doi: 10.1016/0006-291x(77)91549-2. [DOI] [PubMed] [Google Scholar]
- Jones P. B., Galeazzi D. R., Fisher J. M., Whitlock J. P., Jr Control of cytochrome P1-450 gene expression by dioxin. Science. 1985 Mar 22;227(4693):1499–1502. doi: 10.1126/science.3856321. [DOI] [PubMed] [Google Scholar]
- Kashimoto T., Miyata H., Kunita S., Tung T. C., Hsu S. T., Chang K. J., Tang S. Y., Ohi G., Nakagawa J., Yamamoto S. Role of polychlorinated dibenzofuran in yusho (PCB poisoning). Arch Environ Health. 1981 Nov-Dec;36(6):321–326. doi: 10.1080/00039896.1981.10667645. [DOI] [PubMed] [Google Scholar]
- Lee L. S., Weinstein I. B. Mechanism of tumor promoter inhibition of cellular binding of epidermal growth factor. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5168–5172. doi: 10.1073/pnas.76.10.5168. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lü Y. C., Wu Y. C. Clinical findings and immunological abnormalities in Yu-Cheng patients. Environ Health Perspect. 1985 Feb;59:17–29. doi: 10.1289/ehp.59-1568085. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Madhukar B. V., Brewster D. W., Matsumura F. Effects of in vivo-administered 2,3,7,8-tetrachlorodibenzo-p-dioxin on receptor binding of epidermal growth factor in the hepatic plasma membrane of rat, guinea pig, mouse, and hamster. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7407–7411. doi: 10.1073/pnas.81.23.7407. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Manchester D. K., Jacoby E. H. Resolution and reconstitution of human placental monooxygenase activity responsive to maternal cigarette smoking. Dev Pharmacol Ther. 1982;5(3-4):162–172. [PubMed] [Google Scholar]
- Mathews H. B., Anderson M. W. Effect of chlorination on the distribution and excretion of polychlorinated biphenyls. Drug Metab Dispos. 1975 Sep-Oct;3(5):371–380. [PubMed] [Google Scholar]
- Nebert D. W., Jensen N. M. The Ah locus: genetic regulation of the metabolism of carcinogens, drugs, and other environmental chemicals by cytochrome P-450-mediated monooxygenases. CRC Crit Rev Biochem. 1979;6(4):401–437. doi: 10.3109/10409237909105427. [DOI] [PubMed] [Google Scholar]
- Norman R. L., Johnson E. F., Muller-Eberhard U. Identification of the major cytochrome P-450 form transplacentally induced in neonatal rabbits by 3,3,7,8-tetrachlorodibenzo-p-dioxin. J Biol Chem. 1978 Dec 10;253(23):8640–8647. [PubMed] [Google Scholar]
- Pasanen M., Pelkonen O. Solubilization and partial purification of human placental cytochromes P-450. Biochem Biophys Res Commun. 1981 Dec 31;103(4):1310–1317. doi: 10.1016/0006-291x(81)90265-5. [DOI] [PubMed] [Google Scholar]
- Pelkonen O., Moilanen M. L. The specificity and multiplicity of human placental xenobiotic-metabolizing monooxygenase system studied by potential substrates, inhibitors and gel electrophoresis. Med Biol. 1979 Oct;57(5):306–312. [PubMed] [Google Scholar]
- Poland A., Glover E., Kende A. S. Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol. Evidence that the binding species is receptor for induction of aryl hydrocarbon hydroxylase. J Biol Chem. 1976 Aug 25;251(16):4936–4946. [PubMed] [Google Scholar]
- Rogan W. J. PCBs and cola-colored babies: Japan, 1968, and Taiwan, 1979. Teratology. 1982 Dec;26(3):259–261. doi: 10.1002/tera.1420260307. [DOI] [PubMed] [Google Scholar]
- Sunahara G. I., Nelson K. G., Wong T. K., Lucier G. W. Decreased human birth weights after in utero exposure to PCBs and PCDFs are associated with decreased placental EGF-stimulated receptor autophosphorylation capacity. Mol Pharmacol. 1987 Nov;32(5):572–578. [PubMed] [Google Scholar]
- Tierney B., Weaver D., Heintz N. H., Schaeffer W. I., Bresnick E. The identity and nuclear uptake of a cytosolic binding protein for 3-methylcholanthrene. Arch Biochem Biophys. 1980 Apr 1;200(2):513–523. doi: 10.1016/0003-9861(80)90383-5. [DOI] [PubMed] [Google Scholar]
- Vickers A. E., Sloop T. C., Lucier G. W. Mechanism of action of toxic halogenated aromatics. Environ Health Perspect. 1985 Feb;59:121–128. doi: 10.1289/ehp.59-1568090. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Welch R. M., Harrison Y. E., Conney A. H., Poppers P. J., Finster M. Cigarette smoking: stimulatory effect on metabolism of 3,4-benzpyrene by enzymes in human placenta. Science. 1968 May 3;160(3827):541–542. doi: 10.1126/science.160.3827.541. [DOI] [PubMed] [Google Scholar]
- Whitlock J. P., Jr, Galeazzi D. R. 2,3,7,8-Tetrachlorodibenzo-p-dioxin receptors in wild type and variant mouse hepatoma cells. Nuclear location and strength of nuclear binding. J Biol Chem. 1984 Jan 25;259(2):980–985. [PubMed] [Google Scholar]
- Wong T. K., Domin B. A., Bent P. E., Blanton T. E., Anderson M. W., Philpot R. M. Correlation of placental microsomal activities with protein detected by antibodies to rabbit cytochrome P-450 isozyme 6 in preparations from humans exposed to polychlorinated biphenyls, quaterphenyls, and dibenzofurans. Cancer Res. 1986 Feb;46(2):999–1004. [PubMed] [Google Scholar]
- Wong T. K., Everson R. B., Hsu S. T. Potent induction of human placental mono-oxygenase activity by previous dietary exposure to polychlorinated biphenyls and their thermal degradation products. Lancet. 1985 Mar 30;1(8431):721–724. doi: 10.1016/s0140-6736(85)91264-4. [DOI] [PubMed] [Google Scholar]
- Wong T. K., Sloop T., Lucier G. W. Nondetectable concentrations of human placental Ah receptors are associated with potent induction of microsomal benzo[a]pyrene hydroxylase in individuals exposed to polychlorinated biphenyls, quaterphenyls, and dibenzofurans. Toxicol Appl Pharmacol. 1986 Aug;85(1):60–68. doi: 10.1016/0041-008x(86)90387-x. [DOI] [PubMed] [Google Scholar]
