Fourteen-day oral combination dose toxicity study of CGS 16949A (aromatase inhibitor) with 5-fluorouracil or tamoxifen in rats

Journal of Toxicological Sciences

Volumn 22, Issue 1, 1997, Pages 1-24

  Matsuda, Akitaka ^a   Higuchi, Kazuhiro ^a   Karasawa, Michiyo ^a   Yoneyama, Shigeki ^a   Deguchi, Jiro ^b   Miyamoto, Masaki ^b  

^a N   (Japan)

^b CIBA GEIGY LTD   (Switzerland)

Author keywords

5 Fluorouracil; Aromatase; CGS 16949A; Estrogen; Tamoxifen

Indexed keywords

AROMATASE INHIBITOR; FADROZOLE; FLUOROURACIL; TAMOXIFEN;

ADOLESCENT; ANIMAL TISSUE; ARTICLE; BREAST CANCER; CONTROLLED STUDY; DRUG EFFECT; DRUG SAFETY; FEMALE; FOOD INTAKE; HISTOPATHOLOGY; NONHUMAN; ORAL DRUG ADMINISTRATION; RAT; WEIGHT GAIN;

EID: 0030936753     PISSN: 03881350     EISSN: 18803989     Source Type: Journal    
DOI: 10.2131/jts.22.1     Document Type: Article

References (21)

1. Bhatanagar, A.S., Schieweck, K., Hausler, A., Brown, L.J. and Steele, R.E. (1989): Inhibitors of estrogen biosynthesis: preclinical studies with CGS 16949A, a new nonsteroidal aromatase inhibitor. Proc. Royal Soc. Edin., 95B, 293.
2. Browne, L.J. and Steele, R.E. (1989): Inhibitors of oestrogen biosynthesis: preclinical studies with CGS 16949A, a new nonsteroidal aromatase inhibitor. Proc. Royal Soc. Edin., 95B, 293-303.
3. Dunnett, C.W.(1955): A multiple comparison procedure for comparing several treatment with a control. J. Am. Statist. Assoc., 50, 1096-1121.
4. Dunnett, C.W.(1964). New tables for multiple comparison with a control. Biometrics, 20, 482-491.
5. Furr, B.J.A. and Jordan, V.C. (1984): The pharmacology and clinical uses of tamoxifen. Pharmacol. Ther., 25, 127-205.
6. Gad, S.C. and Weil, C.S. (1984): Statistics for toxicologists, In Principles and methods of toxicology (Hayes, A.W.ed.), Student ed., PP · 273-320 Raven Press, New York.
7. Gopinath, C., Rombout, P.J.A. and Van Versendaal, R.G. (1978): Serum alkaline phosphatase elevation in female rats treated with ethinyl estradiol. Toxicol., 10, 91-102.
8. Gunson, D.E., Steele, R.E. and Chau, R.Y. (1995): Prevention of spontaneous tumors in female rats by fadrozole hydrochloride, an aromatase inhibitor. Br. J. Cancer, 72, 72-75
9. Houjou, T. and Wada, T. (1991): Antitumor effects and endocrine behavior of new non-steroidal aromatase inhibitor on DMBA-induced rat mammary tumor. J. Jpn. Soc. Cancer Ther 26(8):1519-1526.
10. Kangas, L. (1992): Agonistic and antagonistic effects of antiestrogens in different target organs. Acta Oncol., 31, 143-146.
11. Kubo, K., Tamura, Z., Usami, H., Takeda, S., Suzuki, T., Ninomiya, E. and Isobe, K. (1973): The antitumor effect and toxicity of orally administered 5-fluorouracil. Med. Biol. (Igaku to Seibutsugaku), 86, 77-81 (in Japanese).
12. Kruskal, W.H. and Wallis, W.A. ( 1952): Use of ranks in one-criterion variance analysis. J. Am. Statist. Assoc., 47, 583-621.
13. Miyazaki, H., Imamura, S., Koyama, K., Hara, T., Nishikawa, S., Shiramizu, K., Ohguro, Y. and Shimizu, M. (1974): Safety evaluation of oral 5-fluorouracil (acute, subacute, chronic toxicity and teratological studies). Clin. Report (Kiso to Rinshou), 8, 2603-2636 (in Japanese).
14. Nagae, Y, Miyamoto, M. and Miyamoto, H. (1991): Effects of estrogen replacement on liver function in ovariectomized rats. J. Toxicol. Sci., 16, 87-100.
15. Nagae, Y., Takahashi, S., Takahashi, H., Deguchi, J., Yasuda, S., Kawahara, M., Mori, T. and Miyamoto, M. (1992): A 3-month subacute toxicity study of 17 β -estradiol by continuously subcutaneous infusion in ovariectomized rats. Jpn. Pharmacol. Ther., 20, 10, 37-51.
16. Schieweck, K., Bhatanagar, A.S. and Matter, A. (1988): CGS 16949A, a new nonsteroidal aromatase inhibitor: Effects on hormone-dependent and independent tumors in vivo. Cancer Res., 48, 834-838.
17. Sheff́e, H. (1953): A method for judging all contrasts in the analysis of variance. Biometrika, 40, 87-104.
18. Snedecor, G.W. and Cochran, W.G. (1967): Statistical methods, 6th ed., PP · 246-284. Iowa State University Press, Ames, Iowa.
19. Steele, R.E., Mellor, L.B., Sawyer, W.K., Wasvary, J.M. and Brown, L.J. (1987): In vitro and in vivo studies demonstrating potent and selective estrogen inhibition with the nonsteroidal aromatase inhibitor CGS 16949A. Steroids, 50, 147-161.
20. Tanaka, M., Yano, S., Hasegawa, Y. and Nakao, K. (1994): Antiproliferative effect of the new aromatase inhibitor fadrozole on pre-and post-menopausal models of rat mammary tumor. Arzneim. Forsch., 44, 774-778.
21. Tominaga, T., Yoshida, Y., Shinozuka, K., Hayashi, K. and Kosaki, G. (1990): Effect of CGS 16949A plus tamoxifen on induced mammary tumors in rats. Eur. J. Cancer, 26, 600-603.