Dose-threshold for thyroid tumor-promoting effects of xylazine in rats

Toxicology

Volumn 188, Issue 2-3, 2003, Pages 275-283

  Okamura, Miwa ^a   Yasuhara, Kazuo ^b   Koujitani, Takatoshi ^b   Nasu, Masahiro ^c   Hirose, Masao ^b   Mitsumori, Kunitoshi ^a,b  

^a TOKYO UNIVERSITY OF AGRICULTURE AND TECHNOLOGY   (Japan)

^b NATIONAL INSTITUTE OF HEALTH SCIENCES   (Japan)

^c Panapharm Laboratories Co Ltd   (Japan)

Author keywords

Rat; Threshold; Thyroid; Tumor promotion; Xylazine

Indexed keywords

BIS(2 HYDROXYPROPYL)NITROSAMINE; XYLAZINE;

ADENOMA; ANIMAL EXPERIMENT; ARTICLE; CELL HYPERPLASIA; CONTROLLED STUDY; DRUG EFFECT; HISTOPATHOLOGY; LIOTHYRONINE BLOOD LEVEL; MALE; MAXIMUM ALLOWABLE CONCENTRATION; NONHUMAN; OVARY FOLLICLE CELL; PRIORITY JOURNAL; RAT; THYROID WEIGHT; THYROTROPIN BLOOD LEVEL; THYROXINE BLOOD LEVEL; TUMOR PROMOTION;

EID: 0037723073     PISSN: 0300483X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0300-483X(03)00093-3     Document Type: Article

References (24)

1. Chamberlain P.L., Brynes S.D. The regulatory status of xylazine for use in food-producing animals in the United States. J. Vet. Pharmacol. Therap. 21:1998;322-329.
2. Florin I., Rutberg L., Curvall M., Enzell C. Screening of tobacco smoke constituents for mutagenicity using the Ames test. Toxicology. 18:1980;219-232.
3. Galloway S.M., Armstrong M.J., Reuben C., Colman C., Brown B., Cannon C., Bloom A.D., Nakamura F., Ahmed M., Duk S., Rimpo J., Margolin B.H., Resnick M.A., Anderson B., Zeiger E. Chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells: evaluation of 108 chemicals. Environ. Mol. Mutagen. 10:(Suppl. 10):1987;1-175.
4. Greene S.A., Thurmon J.C. Xylazine - a review of its pharmacology and use in veterinary medicine. J. Vet. Pharmacol. Therap. 11:1988;295-313.
5. Gross M.E., Tranquilli W.J. Use of alpha-2-adrenergic receptor antagonists. J. Am. Vet. Med. Assoc. 195:1989;378-381.
6. Hascheck W.M., Rousseaux C.G. Thyroid follicular cells. Fundamentals of Toxicologic Pathology. 1998;418-426 Academic Press, New York. Chapter 14.
7. Hill R.N., Erdreich L.S., Paynter O.E., Roberts P.A., Rosenthal S.L., Wilkinson C.F. Review, thyroid follicular cell carcinogenesis. Fundam. Appl. Toxicol. 12:1989;629-697.
8. Holland D.C., Munns R.K., Roybal J.E., Hurlbut J.A., Long A.R. Simultaneous determination of xylazine and its major metabolite, 2,6-dimethylaniline, in bovine and swine kidney by liquid chromatography. J. AOAC Int. 76:1993;720-724.
9. Hsu S.M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J. Histochem. Cytochem. 29:1981;577-580.
10. Koch-Weser J., Sidel V.W., Dexter M., Parish C., Finer D.C., Kanarek P. Adverse reactions to sulfisoxazole, sulfamethoxazole, and nitrofurantoin. Manifestations and reaction rates during 2118 courses of therapy. Arch. Intern. Med. 128:1971;399-404.
11. Koujitani T., Yasuhara K., Kobayashi H., Shimada A., Onodera H., Takagi H., Hirose M., Mitsumori K. Tumor promoting activity of 2,6-dimethylaniline in a two-stage nasal carcinogenicity model in rats initiated with N-bis(2-hydroxypropyl)nitrosamine. Cancer Lett. 142:1999;161-171.
12. Koujitani T., Yasuhara K., Kobayashi H., Shimada A., Onodera H., Takagi H., Tamura T., Hirose M., Mitsumori K. Absence of tumor promoting activity of xylazine in a two-stage nasal carcinogenesis model in N-bis(2-hydroxypropyl) nitrosamine-treated rats. J. Toxicol. Pathol. 12:1999;203-208.
13. Mutlib A.E., Chui Y.C., Young L.M., Abbott F.S. Characterization of metabolites of xylazine produced in vivo and in vitro by LC/MS/MS and by GC/MS. Drug Metab. Dispos. 20:1992;840-848.
14. National Toxicology Program NTP (1990) Toxicology and carcinogenesis studies of 2,6-xylidine (2,6-dimethylaniline) in Charles River CD rats (feed studies), NTP Technical Report No. 278, US Department of Health and Human Services, Public Health Service, National Institutes of Health, Bethesda, MD.
15. Onodera H., Mitsumori K., Takahashi K., Shimo T., Yasuhara K., Kitaura K., Takahashi M., Hayashi Y. Thyroid proliferative lesions induced by anti-thyroid drugs in rats are not always accompanied by sustained increases in serum TSH. J. Toxicol. Sci. 19:1994;227-234.
16. Rudd C.J., Mitchell A.D., Spalding J. L5178Y mouse lymphoma cell mutagenesis assay of coded chemicals incorporating analyses of the colony size distributions. Environ. Mutagen. 5:1983;419.
17. Shimo T., Mitsumori K., Onodera H., Yasuhara K., Takahashi M., Takahashi M., Ueno Y., Hayashi Y. Time course observation of thyroid proliferative lesions and serum TSH levels in rats treated with thiourea after DHPN-initiation. Cancer Lett. 85:1994;141-149.
18. Swarm R.L., Roberts G.K.S., Levy A.C., Hines L.R. Observation on the thyroid gland in rats following the administration of sulfamethoxazole and trimethoprom. Toxicol. Appl. Pharmacol. 24:1973;351-363.
19. WHO, 1996. Toxicological evaluation of certain veterinary drug residues in food. WHO Food Additives Series, 876, World Health Organization, Geneva.
20. WHO, 1998. Evaluation of certain veterinary drug residues in food. WHO Technical Report Series, 876, World Health Organization, Geneva.
21. Wynford-Thomas D., Stringer B.M.J., Williams E.D. Discussion of growth and function in the rat thyroid during prolonged goitrogen administration. Acta Endocrinol. 101:1982;562-569.
22. Yasuhara K., Kobayashi H., Shimamura Y., Koujitani T., Onodera H., Takagi H., Hirose M., Mitsumori K. Toxicity and blood concentrations of xylazine or its metabolite, 2,6-dimethylaniline, in rats after the single or repeated oral administration. J. Toxicol. Sci. 25:2000;105-113.
23. Yasuhara K., Koujitani T., Takegawa K., Nasu M., Onodera H., Takagi H., Hirose M., Mitsumori K. Promoting effects of xylazine on development of thyroid tumors in rats initiated with N-bis(2-hydroxypropyl)nitrosamine and the mechanism of action. Carcinogenesis. 22:2001;613-618.
24. Zimmer D., Mazurek J., Petzold G., Bhuyan B.K. Bacterial mutagenicity and mammalian cell DNA damage by several substituted anilines. Mutat. Res. 77:1980;317-326.