Toxicological Sciences 62, 166-175 (2001)
Copyright © 2001 by the Society of Toxicology
SAFETY EVALUATION |
Hepatic Vitamin A Depletion Is a Sensitive Marker of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Exposure in Four Rodent Species
Institute of Environmental Medicine, Karolinska Institutet, PO Box 210, S-171 77 Stockholm, Sweden
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-treated animals show altered retinoid homeostasis and exhibit signs of toxicity similar to those of vitamin A–deficient animals. In this study we established dose-response curves for sublethal oral doses of TCDD and hepatic vitamin A gain in four rodent species. This was done to evaluate any potential correlation between decreased hepatic vitamin A gain and other TCDD-induced effects, particularly depressed body weight gain and hepatic CYP1A induction. Young Hartley guinea pigs, Sprague-Dawley rats, C57BL/6 mice, and Golden Syrian hamsters were given single oral doses of TCDD at up to 2.5, 100, 1000, and 1000 µg/kg bw, respectively, and killed 28 days after treatment. Hepatic vitamin A gain was decreased 25% compared to controls at estimated doses of 0.1, 0.9, 1.1 and 3.6 µg/kg bw in guinea pigs, hamsters, rats, and mice, respectively. CYP1A induction and hepatic vitamin A gain were affected at similar dose levels and showed similar, but inverse dose-response curves in each of the four species, consistent with the hypothesis that altered vitamin A homeostasis is Ah-receptor mediated. In addition, there was an apparent correlation between the dose-response curves for decreased hepatic vitamin A gain and decreased body weight gain in all species. Taken together with the known importance of vitamin A in body weight regulation, this result was consistent with a contributing role for altered retinoid homeostasis in the wasting syndrome induced by TCDD.
Key Words: 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD, vitamin A; retinoids; wasting; EROD; species; hepatic; renal.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. N'Jai, D. R. Boverhof, E. Dere, L. D. Burgoon, Y. S. Tan, J. C. Rowlands, R. A. Budinsky, K. E. Stebbins, and T. R. Zacharewski Comparative Temporal Toxicogenomic Analysis of TCDD- and TCDF-Mediated Hepatic Effects in Immature Female C57BL/6 Mice Toxicol. Sci., June 1, 2008; 103(2): 285 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Singhal, K. Shankar, T. M. Badger, and M. J. Ronis Estrogenic status modulates aryl hydrocarbon receptor--mediated hepatic gene expression and carcinogenicity Carcinogenesis, February 1, 2008; 29(2): 227 - 236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. J. Walker, K. Yoshizawa, R. A. Miller, A. E. Brix, D. M. Sells, M. P. Jokinen, M. E. Wyde, M. Easterling, and A. Nyska Pulmonary Lesions in Female Harlan Sprague-Dawley Rats Following Two-Year Oral Treatment with Dioxin-Like Compounds Toxicol Pathol, December 1, 2007; 35(7): 880 - 889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Boverhof, L. D. Burgoon, C. Tashiro, B. Sharratt, B. Chittim, J. R. Harkema, D. L. Mendrick, and T. R. Zacharewski Comparative Toxicogenomic Analysis of the Hepatotoxic Effects of TCDD in Sprague Dawley Rats and C57BL/6 Mice Toxicol. Sci., December 1, 2006; 94(2): 398 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Fletcher, N. Giese, C. Schmidt, N. Stern, P. M. Lind, M. Viluksela, J. T. Tuomisto, J. Tuomisto, H. Nau, and H. Hakansson Altered Retinoid Metabolism in Female Long-Evans and Han/Wistar Rats following Long-Term 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD)-Treatment Toxicol. Sci., August 1, 2005; 86(2): 264 - 272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Boverhof, L. D. Burgoon, C. Tashiro, B. Chittim, J. R. Harkema, D. B. Jump, and T. R. Zacharewski Temporal and Dose-Dependent Hepatic Gene Expression Patterns in Mice Provide New Insights into TCDD-Mediated Hepatotoxicity Toxicol. Sci., June 1, 2005; 85(2): 1048 - 1063. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-M. Yang, D.-Y. Huang, G.-F. Liu, J.-C. Zhong, K. Du, Y.-F. Li, and X.-H. Song Inhibitory Effects of Vitamin A on TCDD-induced Cytochrome P-450 1A1 Enzyme Activity and Expression Toxicol. Sci., May 1, 2005; 85(1): 727 - 734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Oberg, A. Sjodin, H. Casabona, I. Nordgren, E. Klasson-Wehler, and H. Hakansson Tissue Distribution and Half-Lives of Individual Polychlorinated Biphenyls and Serum Levels of 4-Hydroxy-2,3,3`,4`,5-pentachlorobiphenyl in the Rat Toxicol. Sci., December 1, 2002; 70(2): 171 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Song, M. Clagett-Dame, R. E. Peterson, M. E. Hahn, W. M. Westler, R. R. Sicinski, and H. F. DeLuca A ligand for the aryl hydrocarbon receptor isolated from lung PNAS, November 12, 2002; 99(23): 14694 - 14699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Andersson, J. McGuire, C. Rubio, K. Gradin, M. L. Whitelaw, S. Pettersson, A. Hanberg, and L. Poellinger A constitutively active dioxin/aryl hydrocarbon receptor induces stomach tumors PNAS, July 23, 2002; 99(15): 9990 - 9995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Krig, R. A. S. Chandraratna, M. M. J. Chang, R. Wu, and R. H. Rice Gene-Specific TCDD Suppression of RAR{alpha}- and RXR-Mediated Induction of Tissue Transglutaminase Toxicol. Sci., July 1, 2002; 68(1): 102 - 108. [Abstract] [Full Text] [PDF]
|
|