The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
FOURTEEN-DAY ORAL COMBINATION DOSE TOXICITY STUDY OF CGS; 16949A (AROMATASE INHIBITOR) WITH 5-FLUOROURACIL OR TAMOXIFEN IN RATS
Akitaka MATSUDAKazuhiro HIGUCHIMichiyo KARASAWAShigeki YONEYAMAJiro DEGUCHIMasaki MIYAMOTO
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Keywords: Estrogen
JOURNALS FREE ACCESS

1997 Volume 22 Issue 1 Pages 1-24

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Abstract

CGS 16949A, an aromatase inhibitor, was administered orally to female rats at doses of 1 and 10 mg/kg/day alone and in combination with tamoxifen (0.5 or 5mg/kg/day) or 5-fluorouracil (20 mg-g/day) for 14 days. CGS 16949A and tamoxifen combination: Increased food intake and body weight noted after CGS 16949A treatment were also observed following combination treatment, though to a lesser degree. Most of the clinical pathological features noted following combination treatment were similar to those induced by single compound treatment. Gross pathological and histopathological changes ascribed to the antiestrogenic action of CGS 16949A, such as increased ovarian weight, decreased uterine weight, cystic follicles and atrophied uterus and vaginal epithelium, were alleviated by combination treatment, and were comparable in severity to those caused by tamoxifen alone. No severe toxic changes were induced by combination treatment. CGS 16949A and 5-fluorouracil combination: Increased body weight noted after CGS 16949A treatment was also observed following combination treatment, though to a lesser degree. Most of the changes caused by single compound treatment, including the aforementioned effects of CGS 16949A on the genital organs, were also noted following combination treatment. There was no evidence of enhancement of the effects by combination treatment.

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