Mechanisms of exocrine pancreatic toxicity induced by oral treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Harlan Sprague-Dawley rats

Toxicological Sciences

Volumn 85, Issue 1, 2005, Pages 594-606

  Yoshizawa, Katsuhiko ^a   Marsh, Tiwanda ^a   Foley, Julie F ^a   Cai, Bo ^a   Peddada, Shyamal ^a   Walker, Nigel J ^a   Nyska, Abraham ^a  

^a NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

Author keywords

Acinar cells; Dioxin; Immunohistochemistry; Pancreas; Rat; Vacuolation

Indexed keywords

2,3,7,8 TETRACHLORODIBENZO PARA DIOXIN; AMYLASE; AROMATIC HYDROCARBON RECEPTOR; CHOLECYSTOKININ A RECEPTOR; CHOLECYSTOKININ OCTAPEPTIDE; CORN OIL; CYCLINE; CYTOCHROME P450 1A1; EOSIN; HEMATOXYLIN;

ACINAR CELL; ACINAR CELL CARCINOMA; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; CELL DAMAGE; CELL KINETICS; CELL PROLIFERATION; CELL VACUOLE; CELLULAR DISTRIBUTION; CONTROLLED STUDY; FEMALE; GENE OVEREXPRESSION; HISTOPATHOLOGY; IMMUNOHISTOCHEMISTRY; MOLECULAR MECHANICS; MORPHOMETRICS; NONHUMAN; PANCREAS DISEASE; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; RAT; RAT STRAIN; REVIEW; STAINING; STATISTICAL SIGNIFICANCE;

ADMINISTRATION, ORAL; ANIMALS; APOPTOSIS; DUODENUM; ENVIRONMENTAL POLLUTANTS; FEMALE; IMMUNOHISTOCHEMISTRY; PANCREAS, EXOCRINE; RATS; RATS, INBRED STRAINS; RATS, SPRAGUE-DAWLEY; TETRACHLORODIBENZODIOXIN;

ANIMALIA; ZEA MAYS;

EID: 18144415048     PISSN: 10966080     EISSN: None     Source Type: Journal    
DOI: 10.1093/toxsci/kfi121     Document Type: Review

References (100)

1. Agency for Toxic Substances and Disease Registry (ATSDR). (1998). Toxicological profile for chlorinated dibenzo-p-dioxins. U.S. Department of Health and Human Services, Public Health Service, ATSDR, Atlanta, GA.
2. Alguacil, J., Porta, M., Kauppinen, T., Malats, N., Kogevinas, M., Carrato, A. (2003). Occupational exposure to dyes, metals, polycyclic aromatic hydrocarbons and other agents and K-ras activation in human exocrine pancreatic cancer. Int. J. Cancer 107, 635-641.
3. Andren-Sandberg, A., Hoem, D., and Backman, P. L. (1999). Other risk factors for pancreatic cancer: Hormonal aspects. Ann. Oncol. 10 Suppl. 4, 131-135.
4. Beaussier, M., Wendum, D., Fouassier, L., Rey, C., Barbu, V., Lasnier, E., Lienhart, A., Scoazec, J. Y., Rosmorduc, O., Housset, C. (2005). Adaptative bile duct proliferative response in experimental bile duct ischemia. J. Hepatol. 42, 257-265.
5. Bertazzi, P. A., Consonni, D., Bachetti, S., Rubagotti, M., Baccarelli, A., Zocchetti, C., and Pesatori, A. C. (2001). Health effects of dioxin exposure: A 20-year mortality study. Am. J. Epidemiol. 153, 1031-1044.
6. Biederbick, A., and Elsässer, H-P. (1998). Diurnal pattern of rat pancreatic acinar cell replication. Cell Tissue Res. 291, 277-283.
7. Boorman, G. A., Haseman, J. K., Waters, M. D., Hardisty, J. F., and Sills, R. C. (2002). Quality review procedures necessary for rodent pathology databases and toxicogenomic studies: The National Toxicology Program experience. Toxicol. Pathol. 30, 88-92.
8. Bourassa, J., Laine, J., Kruse, M. L., Gagnon, M. C., Calvo, E., and Morisset, J. (1999). Ontogeny and species differences in the pancreatic expression and localization of the CCK-A receptors. Biochem. Biophys. Res. Commun. 260, 820-828.
9. Brix, A. E., Jokinen, M. P., Walker, N. J., Sells, D. M., and Nyska, A. (2004). Characterization of bronchiolar metaplasia of the alveolar epithelium in female Sprague-Dawley rats exposed to 3,3′,4,4′ 5-pentachlorobiphenyl (PCB 126). Toxicol. Pathol. 32, 333-337.
10. Clarke, J., Flatt, P. R., and Barnett, C. R. (1997). Cytochrome P450 1A-like proteins expressed in the islets of Langerhans and altered pancreatic B-cell secretory responsiveness. Br J. Pharmacol. 121, 389-394.
11. Denison, M. S., and Nagy, S. R. (2003). Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemical. Annu. Rev. Pharmacol. Toxicol. 43, 309-334.
12. Dolwick, K. M., Schmidt, J. V, Carver, L. A., Swanson, H. I., and Bradfield, C. A. (1993). Cloning and expression of a human Ah receptor cDNA. Mol. Pharmacol. 44, 911-917.
13. Fernandez-Salguero, P. M., Hilbert, D. M., Rudikoff, S., Ward, J. M., and Gonzalez, F. J. (1996). Aryl-hydrocarbon receptor-deficient mice are resistant to 2,3,7,8-tetrachloroidibenzo-p-dioxin-induced toxicity. Toxicol. Appl. Pharmacol. 140, 173-179.
14. Fisher, M. T., Nagarkatti, M., and Nagarkatti, P. S. (2004). Combined screening of thymocytes using apoptosis-specific CDNA array and promoter analysis yields novel gene targets mediating TCDD-induced toxicity. Toxicol. Sci. 78, 116-124.
15. Foster, J. R., Idle, J. R., Hardwick, J. P., Bars, R., Scott, P., and Bragana, J. M. (1993). Induction of drug-metabolizing enzymes in human pancreatic cancer and chronic pancreatitis. J. Pathol. 169, 457-463.
16. Fournie, J. W., and Vogelbein, W. K. (1994). Exocrine pancreatic neoplasms in the mummichog (Fundulus heteroclitus) from a creostone-contaminated site. Toxicol. Pathol. 22, 237-247.
17. Furukawa, F., Nishikawa, A, Kasahara, K., Miyauchi, M., Nakamura, H., Son, H. Y., Uchida, K., and Hirose, M. (2001). Involvement of lipid peroxidation in spontaneous pancreatitis in WBN/Kob rats. Pancreas 22, 427-30.
18. Gebhardt, A., Ackermann, W., Unver, N., and Elsasser, H. O. (2004). Expression of galectin-3 in the rat pancreas during regeneration following hormone-induced pancreatitis. Cell Tissue Res. 315, 321-329.
19. Goldsworthy, T. L., Fransson-Steen, R., and Maronpot, R. R. (1996). Importance of and approaches to quantification of hepatocyte apoptosis. Toxicol. Pathol. 24, 24-35.
20. Gonzalez, F. J., and Fernandez-Salguero, P. (1998). The aryl hydrocarbon receptor. Studies using the AHR-null mice. Drug Metab. Dispos. 26, 1194-1198.
21. Gorski, J. R., Muzi, G., Weber, L. W., Pereira, D. W., Arceo, R. J., Iatropoulos, M. J., and Rozman, K. (1988). Some endocrine and morphologival aspects of the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Toxicol. Pathol. 16, 313-320.
22. Greenlee, W. F., Hushka, L. J., and Hushka, D. R. (2001). Molecular basis of dioxin actions: Evidence supporting chemoprotection. Toxicol. Pathol. 29, 6-7.
23. Grossblatt, N. (1996). Guide for the Care and Use of Laboratory Animals. Washington DC: National Academy Press.
24. Hanlon, P. R., Zheng, W., Ko, A. Y., and Jefcoate, C. R. (2004). Identification of novel TCDD-regulated genes by microarray analysis. Toxicol. Appl. Pharmacol. (available online at www.sciencedirect.com).
25. Haschek, W. M., and Rousseaux, C. G. (1998). Exocrine pancreas. In Fundamentals of Toxicologic Pathology (Haschek, W. H. and Rousseaux, C. G., Eds.), pp. 193-204. Academic Press, San Diego, CA.
26. Hassoun, E. A., Wang, H., Abushaban, A., and Stohs, S. J. (2002). Induction of oxidative stress in the tissues of rats after chronic exposure to TCDD, 2,3,4,7,8-pentachlorodibenzofuran, and 3,3′,4,4′,5-pentachlorobiphenyl. J. ToxicoL Environ. Health, A, 65, 825-842.
27. Henry, T. R., Spitsbergen, J. M., Hornung, M. W., Abnet, C. C., and Peterson, R. E. (1997). Early life stage toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in zebrafish (Danio rerio). Toxicol. Appl. Pharmacol. 142, 56-68.
28. Horne, W. I., and Tsukamoto, H. (1993). Dietary modulation of alcohol-induced pancreatic injury. Alcohol 10, 481-484.
29. Imazawa, T., Nishikawa, A., Toyoda, K., Furukawa, F., Mitsui, M., and Hirose, M. (2003). Sequential alteration of apoptosis, p53 expression, and cell proliferation in the rat pancreas treated with 4-hydroxyaminoquinoline 1-oxide. Toxicol. Pathol. 31, 625-631.
30. Jin, B., Kim, G., Park, D. W., and Ryu, D. Y. (2004). Microarray analysis of gene regulation in the Hepa1c1c7 cell line following exposure to the DNA methylation inhibitor 5-aza-2′-deoxycytidine and 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol. In Vitro 18, 659-664.
31. Jokinen, M. P., Walker, N. J., Brix, A. E., Sells, D. M., Haseman, J. K., and Nyska, A. (2003). Increase in cardiovascular pathology in female Sprague-Dawley rats following chronic treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin and 3,3′,4,4′,5-pentchlorobiphenyl. Cardiovasc. Toxicol. 3, 299-310.
32. Keim, V. (2003). Identification of patients with genetic risk factors of pancreatitis: Impact on treatment and cancer prevention. Dig. Dis. 21, 346-350.
33. Kociba, R. J., Keeler, P. A., Park, C. N., Gehring, P. J. (1976). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD): Results of a 13-week oral toxicity study in rats. Toxicol. Appl. Pharmacol. 35, 553-574.
34. Kociba, R. J., Keyes, D. G., Beyer, J. E., Carreon, R. M., Wade, C. E., Dittenber, D. A., Kalnins, R. P., Frauson, L. E., Park, C. N., Barnard, S. D., et al. (1978). Results of a two-year chronic toxicity and oncologenicity study of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats. Toxicol. Appl. Pharmacol. 46, 279-303.
35. Koliopanos, A., Kleeff, J., Xiao, Y., Safe, S., Zimmermann, A. Buchler, M. W., and Friess, H. (2002). Increased arylhydrocarbon receptor expression offers a potential therapeutic target for pancreatic cancer. Oncogene 21, 6059-6070.
36. Kurosawa, H., Miyasaka, K., and Kitani, K. (1989). Influence of bile flow obstruction vs bile diversion on pancreatic secretion in the conscious rat. Int. J. Pancreatol. 4, 187-197.
37. Lee, H-M., He, Q., Englander, E. W., and Greeley, G. H. (2000). Endocrine disruptive effects of polychlorinated aromatic hydrocarbons on intestinal cholecystokinin in rats. Endocrinology 141, 2938-2944.
38. Lin, R. S., and Kessler, I. I. (1981). A multifactorial model for pancreatic cancer in man. J.A.M.A. 245, 147-152.
39. Longnecker, D. S., and Sumi, C. (1990). Effects of sex steroid hormones on pancreatic cancer in the rat. Int. J. Pancreatol. 7, 159-165.
40. Maronpot, R. R., Foley, J. E, Takahashi, K., Goldsworthy, T., Clark, G., Tritscher, A., Portier, C., and Lucier, G. (1993). Dose response for TCDD promotion of hepatocarcinogenesis in rats initiated with DEN: Histologic, biochemical, and cell proliferation endpoints. Environ. Health Perspect. 101, 634-642.
41. Martinez, J. M., Afshari, C. A., Bushel, P. R., Masuda, A., Takahashi, T., and Walker, N. J. (2002). Differential toxicogenomic responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin in malignant and nonmalignant human airway epithelial cells. Toxicol. Sci. 69, 409-423.
42. Matsumura, F. (2003). On the significance of the role of cellular stress response reactions in the toxic actions of dioxin. Biochem. Pharmacol. 66, 527-540.
43. Meijers, M., Appel, M. J., van Garderen-Hoetmer, A., Lamers, C. B. H., Rovati, L. C., Jansen, J. B., and Woutersen, R. A. (1992). Effects of cholecystokinin and bombesin on development of azaserine-induced pancreatic tumours in rats: Modulation by the cholecystokinin receptor antagonist lorglumide. Carcinogenesis 13, 1525-1528.
44. Milham, S., Jr., and Demers, R. Y (1984). Mortality among pulp and paper workers. J. Occup. Med. 26, 844-846.
45. Monstein, H. J., Nylander, A. G., Salehi, A., Chen, D., Lundquist, I., and Hakanson, R. (1996). Cholecystokinin-A and cholecystokinin-B/gastrin receptor MRNA expression in the gastrointestinal tract and pancreas of the rat and man. A polymerase chain reaction study. Scand. J. Gastroenterol. 31, 383-390.
46. Moralejo, D. H., Ogino, T., Kose, H., Yamada, T., and Matsumoto, K. (2001). Genetic verification of the role of CCK-AR in pancreatic proliferation and blood glucose and insulin regulation using a congenic rat carrying CCK-AR null allele. Res. Commun. Mol. Pathol. Pharmacol. 109, 259-274.
47. National Toxicology Program (2004a). Toxicology and carcinogenesis studies of a mixture of 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) (CAS No. 57465-28-8) and 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) in female Harlan Sprague-Dawley rats (gavage studies). TR530. Research Triangle Park, NC.
48. National Toxicology Program (2004b). Toxicology and carcinogenesis studies of a mixture of 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) (CAS No. 57465-28-8) and 2,3′,4,4′,5-pentachlorobiphenyl (PCB 118) (CAS No. 31508-00-6) in female Harlan Sprague-Dawley rats (gavage studies) TR531. Research Triangle Park, NC.
49. National Toxicology Program (2004c). Toxicology and carcinogenesis studies of a mixture of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (CAS No. 1746-01-6), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) (CAS No. 57117-31-4), and 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) (CAS No. 57465-28-8) in female Harlan Sprague-Dawley rats (gavage studies). TR526. Research Triangle Park, NC.
50. National Toxicology Program (2004d). Toxicology and carcinogenesis studies of 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) (CAS No. 57065-27-1) in female Harlan Sprague-Dawley rats (gavage studies) TR529. Research Triangle Park, NC.
51. National Toxicology Program (2004e). Toxicology and carcinogenesis studies of 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) (CAS No. 57465-28-8) in female Harlan Sprague-Dawley rats (gavage studies). TR520. Research Triangle Park, NC.
52. National Toxicology Program (2004f). Toxicology and carcinogenesis studies of 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) (CAS No. 57117-31-4) in female Harlan Sprague-Dawley rats (gavage studies). TR525. Research Triangle Park, NC.
53. National Toxicology Program (2004g). Toxicology and carcinogenesis studies of 2,3,7,8-tetrachloribenzo-p-dioxin (TCDD) (CAS No. 1746-01-6) in female Harlan Sprague-Dawley rats (gavage studies). TR521. Research Triangle Park, NC.
54. Nebert, D. W., Dalton, T. P, Okey, A. B., and Gonzalez, F. J. (2004). Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer. J. BioL Chem. 279, 23847-23850.
55. Nyska, A., Jokinen, M. P., Brix, A. E., Sells, D. M., Wyde, M. E., Orzech, D., Haseman, J. K., Flake, G., and Walker, N. J. (2004). Exocrine pancreatic pathology in female Harlan Sprague-Dawley rats following chronic treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin-like compounds. [i Environ. Health Perspect. 112, 903-909.
56. Obourn, J. D., Frame, S. R., Chiu, T., Solomon, T. E., and Cook, J. C. (1997a). Evidence that A8947 enhances pancreas growth via trypsin inhibitor mechanism. Toxicol. Appl. Pharmacol. 146, 116-126.
57. Obourn, J. D., Frame, S. R., Bell, Jr., R. H., Longnecker, D. S., Elliott, G. S., and Cook, J. C. (1997b). Mechanisms for the pancreatic oncogenic effects of the peroxisome proliferators Wyeth-14,643. Toxicol. Appl. Pharmacol 145, 425-436.
58. Ohlsson, B., Axelson, J., Sternby, B., Rehfeld, J. E, and Ihse, I.(1995). Time-course of the pancreatic changes following long-term stimulation or inhibition of the CCK-A receptor. Int. J. Pancreatol. 18, 59-66.
59. Ohlsson, B., Borg, K., Mulder, H., Rehfeld, J. F., Axelson, J., and Sundler, F. (2000). Continuous infusion of cholecystokinin leads to down-regulation of the cholecystokinin-A receptor in the rat pancreas. Scand. J. Gastroenterol. 35, 612-618.
60. Ojajarvi, J. A., Partanen, T. J., Ahlbom, A., Boffetta, P., Hakulinen, T., Jourenkova, N., Kauppinen, T. P., Kogevinas, M., Porta, M., Vainio, H. U., et al. (2000). Occupational exposures and pancreatic cancer: A meta-analysis. Occup. Environ. Med. 57, 316-324.
61. Ojajarvi, A., Partanen, T., Ahlbom, A., Boffetta, P., Hakulinen, T., Jourenkova, N., Kauppinen, T., Kogevinas, M., Vainio, H., Weiderpass, E., et al. (2001). Risk of pancreatic cancer in workers exposed to chlorinated hydrocarbon solvents and related compounds: A meta-analysis. Am. J. Epidemiol. 153, 841-850.
62. Ortiz-Delgado, J. B., and Sarasquete, C. (2004). Toxicity, histopathological alterations and immunohistochemical CYP1A induction in the early life stages of the seabream, Sparus aurata, following waterborne exposure to B(a)P and TCDD. J. Mol. Histol. 35, 29-45.
63. Panozzo, M. P., Basso, D., Plebani, M., Valente, M. L., Rasia, E., and Balint, L. (1995). Effects of pancreaticobiliary duct obstruction on the exocrine and endocrine rat pancreas. Pancreas 11, 408-414.
64. Pohjanvirta, R., and Tuomisto, J. (1994). Short-term toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxinin laboratory animals: Effects, mechanisms and animal models. Pharmacol. Rev. 46, 483-549.
65. Poland, A., and Knutson, J. C. (1982). 2,3,7,8-tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: Examination of the mechanism of toxicity. Annu. Rev. Pharmacol. Toxicol. 22, 517-554.
66. Pollenz, R. S. (2002). The mechanism of AH receptor protein down-regulation (degradation) and its impact on AH receptor-mediated gene regulation. Chem. Biol. Interact. 141, 41-61.
67. Pollenz, R. S., Santostefano, M. J., Klett, E., Richardson, V. M., Necela, B., and Birnbaum, L. S. (1998). Female Sprague-Dawley rats exposed to a single oral dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin exhibit sustained depletion of aryl hydrocarbon receptor protein in liver, spleen, thymus, and lung. Toxicol. Sci. 42, 117-128.
68. Pollenz, R. S., Sattler, C. A., and Poland, A. (1994). The aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator protein show distinct subcellular localizations in Hepa 1c1c7 cells by immunofluorescence microscopy. Mol. Pharmacol. 45,428-438.
69. Puga, A., Maier, A., and Medvedovic, M. (2000). The transcriptional signature of dioxin in human hepatoma HepG2 cells. Biochem. Pharmacol. 60, 1129-1142.
70. Rao, M. S., and Subbarao, V. (1995). Incidence of pancreatic and testicular tumors in rats treated with ciprofibrate, a peroxisome proliferator. Cancer Lett. 97, 185-188.
71. Robles-Diaz, G., and Duarte-Rojo, A. (2001). Pancreas: A sex steroid-dependent tissue. Isr Med. Assoc. J. 3, 364-368.
72. Roebuck, B. D., Kaplita, P. V., Edwards, B. R., and Praissman, M. (1987). Effects of dietary fats and soybean protein on azaserine-induced pancreatic carcinogenesis and plasma cholecystokinin in the rat. Cancer Res. 47, 1333-1338.
73. Safe, S. (2001). Molecular biology of the Ah receptor and its role in carcinogenesis, Toxicol, Lett. 120, 1-7.
74. Safe, S., and McDougal, A. (2002). Mechanism of action and development of selective aryl hydrocarbon receptor modulators for treatment of hormone-dependent cancers (Review). Int, J. Oncol. 20, 1123-1128.
75. Safe, S., and Wormke, M. (2003). Inhibitory aryl hydrocarbon receptor-estrogen receptor α cross-talk and mechanisms of action. Chem. Res. Toxicol. 16, 807-816.
76. Scarpelli, D. G., Subbarao, V., and Rao, M. S. (1986). Pancreatic lesions induced by a singla dose of N-nitrosobis(2-oxopropyl) amine and selection by resistance to cytotoxicity. Toxicol. Pathol. 14, 324-330.
77. Schmidt, J. V., and Bradfield, C. A. (1996). Ah receptor signaling pathway. Annu. Rev. Cell Dev. Biol. 12, 55-89.
78. Smith, A. G., Clothier, B., Carthew, P., Childs, N. L., Sinclair, P. R., Nebert, D. W., and Dalton, T. P. (2001). Protection of the Cypla2(-/-) null mouse against uroporphyria and hepatic injury following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol. Appl. Pharmacol 173, 89-98.
79. Spitsbergen, J. M., Kleeman, J. M., and Peterson, R. E. (1988). Morphologic lesions and acute in rainbow trout (Salmo gairdneri) treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin. J. Toxicol. Environ. Health 23, 333-358.
80. Stace, N. H., Palmer, T. J., Vaja, S., and Dowling, R. H. (1987). Longterm pancreaticobiliary diversion stimulates hyperplastic and adenomatous nodules in the rat pancreas: A new model for spontaneous tumour formation. Gut 28 Suppl, 265-268.
81. Standop, J., Schneider, M., Ulrich, A., Buchler, M. W., and Pour, P. M. (2003). Differences in immunohistochemical expression of xenobiotic-metabolizing enzymes between normal pancreas, chronic pancreatitis and pancreatic cancer. Toxicol. Pathol. 31, 506-513.
82. Standop, J., Schneider, B. M., Urich, A., Chauhan, S., Moniaux, N., Buchler, M. W., Batra, S. K., and Pour, P. M. (2002). The pattern of xenobiotic-metabolizing enzymes in the human pancreas. J. Toxicol. Environ. Health Part A 65, 1379-1400.
83. Steenland, K., Deddens, J., and Piacitelli, L. (2001). Risk assessment for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) based on an epidemiologic study. Am. J. Epidemiol. 154, 451-458.
84. Steenland, K., Piacitelli, L., Deddens, J., Fingerhunt, M., and Chang, L. I. (1999). Cancer, heart disease, and diabetes in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. J. Natl. Cancer Inst. 91, 779-786.
85. Tang, C., Biemond, I., and Lamers, C. B. H. W. (1996). Cholecystokinin receptors in human pancreas and gallbladder muscle: A comparative study. Gastroenterology 111, 1621-1626.
86. Tangoku, A., Chowdhury, P., Huang, Y. S., Doi, R., Blevins, G. T., Jr., Eyiuche, C., McKay, D. W., and Rayford, P. L. (1992). Exocrine pancreatic function in obstructive jaundice rats: Studies with isolated dispersed pancreatic acini. J. Surg. Res. 53, 378-383.
87. Tani, Y., Maronpot, R. R., Foley, J. F., Haseman, J. K., Walker, N.J., and Nyska, A. (2004). Follicular epithelial cell hypertrophy induced by chronic oral administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Harlan Sprague-Dawley rats. Toxicol. Pathol. 32, 41-49.
88. Tapp, R., L, (1970). Anoxic and secretory vaculation in the acinar cells of the pancreas. Q. J. Exp. Physiol. 55, 1-15.
89. Toyoshiba, H., Walker, N. J., Bailer, A. J., and Portier, C. J. (2004). Evaluation of toxic equivalency factors for induction of cytochromes P450 CYP1A1 and CYP1A2 enzyme activity by dioxin-like compounds. Toxicol. Appl. Pharmacol. 194, 156-168.
90. Ulrich, A. B., Standop, J., Schmied, B. M., Schneider, M. B., Lawson, T. A., and Pour, P. M. (2002). Species difference in the distribution of drug-metabolizing enzymes in the pancreas. Toxicol. Pathol. 30, 247-253.
91. Varga, G., Kisfalvi, K., Pelosini, I., D'Amato, M., and Scarpignato, C. (1998). Different actions of CCK on pancreatic and gastric growth in the rat: Effect of CCKA receptor blockade. Br. J. Pharmacol. 124, 435-440.
92. Walker, N. I., Winterford, C. M., Williamson, R. M., and Kerr, J. F. R. (1993), Ethionine-induced atrophy of rat pancreas involves apoptosis of acinar cells. Pancreas 8, 443-449.
93. Walker, N. J., Crockett, P., Nyska, A., Brix, A., Jokinen, M. P., Sells, D. M., Hailey, J. R., Easterling, M., Haseman, J. K., Yin, M., et al. (2004). Dose-additive carcinogenicity of a defined mixture of "dioxin-like compounds". Environ. Health Perspect., doi:10.1289/ehp.7351 (available at http://dx.doi.org/).
94. Wank, S. A. (1995). Cholecystokinin receptors. Am. J. Physiol. 269, G628-G646.
95. Ward, J. M., Uno, H., Kurata, Y., Weghorst, C. M., and Jang, J-J. (1993). Cell proliferation not associated with carcinogenesis in rodents and humans. Environ. Health Perspect. 101, 125-136.
96. Whitcomb, D. C. (2004). Inflammation and Cancer V. Chronic pancreatitis and pancreatic cancer. Am. J. Physiol. Gastrointest. Liver Physiol. 287, G315-G319.
97. Wilson, J. D., Miller, H., Gelboin, H. V., and Friedman, F. K. (1990). Variation in inducibility of cytochrome P-450c and aryl hydrocarbon hydroxylase in rat liver, lung, kidney, pancreas and nasopharynx. Pharmacology 41, 256-262.
98. Xu, W., Liu, L. Z., Loizidou, M., Ahmed, M., and Charles, I. G. (2002). The role of nitric oxide in cancer. Cell Res. 12, 311-320.
99. Yamamoto, J., Ihara, K., Nakayama, H., Hikino, S., Satoh, K., Kubo, N., Iida, T., Fujii, Y., and Hara, T. (2004). Characteristics expression of aryl hydrocarbon receptor repressor gene in human tissues: Organ-specific distribution and variable induction patterns in mononuclear cells. Life Sci. 74, 1039-1049.
100. Yoshizawa, K., Walker, N. J., Jokinen, M. P., Brix, A. E., Sells, D. M., Marsh, T., Wyde, M. E., Orzech, D., Haseman, J. K., and Nyska, A. (2005). Gingival carcinogenicity in female Harlan Sprague-Dawley rats following two-year oral treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin-like compounds. Toxicol. Sci. 83, 64-67.