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Toxicological Sciences 69, 49-59 (2002)
Copyright © 2002 by the Society of Toxicology

ENDOCRINE TOXICOLOGY

DNA Arrays to Monitor Gene Expression in Rat Blood and Uterus following 17ß-Estradiol Exposure: Biomonitoring Environmental Effects Using Surrogate Tissues

John C. Rockett1, Robert J. Kavlock, Christy R. Lambright, Louise G. Parks, Judith E. Schmid, Vickie S. Wilson, Carmen Wood and David J. Dix

Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711

We propose that gene expression changes in accessible tissues such as blood often reflect those in inaccessible tissues, thus offering a convenient biomonitoring method to provide insight into the effects of environmental toxicants on such tissues. In this pilot study, gene expression changes in peripheral blood leukocytes (PBL) were compared to those in the uteri of adult rats to identify genes that were altered in both tissues following estradiol treatment. Ovariectomized rats were treated with either 17ß-estradiol or vehicle control (corn oil) for 3 days. PBL and uterine RNAs were hybridized to arrays containing 1185 genes. One hundred and ninety three genes were expressed in common between the PBL and uterus. Eighteen were changed significantly in both tissues, 9 of which were treatment- but not tissue-specific (e.g., jun-D, phospholipase A2, thymidine kinase). These results demonstrate that many genes are coexpressed between PBL and uterus, and that some are coregulated by estradiol. Given the limited number of genes examined in this study and the estimated size of other mammalian genomes, we conclude that many more genes will also be coregulated and suggest that accessible tissues such as PBL can serve as surrogate tissues for observing gene expression changes in inaccessible target tissues.

Key Words: uterus; blood; rat; microarray; gene expression; estradiol; endocrine disrupting chemical; biomonitoring; surrogate tissue.


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