Subchronic toxicity and toxicogenomic evaluation of tamoxifen citrate + bexarotene in female rats.

Subchronic toxicity and toxicogenomic evaluation of tamoxifen citrate + bexarotene in female rats. Research Abstract Details 

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Subchronic toxicity and toxicogenomic evaluation of tamoxifen citrate + bexarotene in female rats. Abstract Text:

Thomas L Horn,Karen E O Torres,Jennifer M Naylor,Michael J Cwik,Carol J Detrisac,Izet M Kapetanovic,Ronald A Lubet,James A Crowell,David L McCormick,

Tamoxifen (TAM) is a nonsteroidal antiestrogen that prevents estrogen receptor-positive breast cancer in rodents and humans. Bexarotene (BEX), a selective agonist for retinoid X receptors, inhibits mammary carcinogenesis in rodents. The present study was conducted to support the preclinical development of TAM (tamoxifen citrate) + BEX for use in breast cancer chemoprevention, and to investigate the influence of these agents on hepatic gene expression. Female CD rats (20 per group) received daily oral (gavage) exposure to TAM (0 or 60 microg/kg/day) and/or BEX (0, 5, 15, or 45 mg/kg/day) for a minimum of 90 days. BEX induced mild, dose-related anemia and dose-related increases in serum alkaline phosphatase, cholesterol, triglycerides, and calcium levels, and increased platelet counts. TAM had no biologically significant effect on any clinical pathology parameter and did not alter the effects of BEX on these endpoints. Microscopic alterations induced by BEX included epidermal hyperplasia, hyperkeratosis (stomach), and cytoplasmic clearing (liver). Microscopic changes in TAM-treated rats were limited to mucous cell hypertrophy in the cervix and vagina. The toxicity of administration of the combination of TAM + BEX can generally be predicted on the basis of the toxicity of each drug as a single agent. BEX induced dose-related alterations in the expression of several genes involved in steroid, drug, and/or fatty acid metabolism; TAM did not alter these effects of BEX. Differential expression of genes involved in drug and lipid metabolism may underlie the observed effects of BEX on cholesterol and triglyceride levels and its effects on liver histology.

Subchronic toxicity and toxicogenomic evaluation of tamoxifen citrate + bexarotene in female rats. Publishing Authors By Initials

TL Horn,KE Torres,JM Naylor,MJ Cwik,CJ Detrisac,IM Kapetanovic,RA Lubet,JA Crowell,DL McCormick,

For similar biological sciences: biology: genetics: pharmacogenetics: toxicogenetics research abstracts see: biological sciences: biology: genetics: pharmacogenetics: toxicogenetics research

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Subchronic toxicity and toxicogenomic evaluation of tamoxifen citrate + bexarotene in female rats. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Toxicological sciences : an official journal of th

VOLUME: 99

Page Numbers: 612-27

Journal Abbreviation: Toxicol. Sci.

ISSN: 1096-6080

DAY: 14

MONTH: 07

YEAR: 2007

Subchronic toxicity and toxicogenomic evaluation of tamoxifen citrate + bexarotene in female rats. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9805461

Subchronic toxicity and toxicogenomic evaluation of tamoxifen citrate + bexarotene in female rats. Keywords Mesh Terms:

KEYWORDS: Toxicogenetics

MESH TERMS: toxicity

Chemical & Substance for Abstract: Subchronic toxicity and toxicogenomic evaluation of tamoxifen citrate + bexarotene in female rats. Information

Substance Name: Tamoxifen

Registry Number: 10540-29-1

Grant and Affiliation Information for Subchronic toxicity and toxicogenomic evaluation of tamoxifen citrate + bexarotene in female rats.

AFFILIATION: Life Sciences Group, IIT Research Institute, Chicago, Illinois 60616, USA.

Country: United States

AGENCY: United States NCI

GRANT: N01-CN-43304

ACRONYM: CN

MEDLINETA: Toxicol Sci

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