| Long-Term Effects of Neonatal Exposure to Hydroxylated Polychlorinated Biphenyls in the BALB/cCrgl Mouse Jeanelle M. Martinez,1 L. Clifton Stephens,2 and Lovell
A. Jones1 1Department of Gynecologic Oncology and 2Department of
Veterinary Medicine and Surgery, University of Texas, M.D. Anderson Cancer
Center, Houston, Texas, USA Abstract
The neonatal mouse model has been a valuable tool in determining the long-term effects of early exposure to estrogenic agents in mammals. Using this model, we compared the effects of 2´,4´,6´-trichloro-4-biphenylol (OH-PCB-30) and 2´,3´,4´,5´-tetrachloro-4-biphenylol (OH-PCB-61) as prototype estrogenic hydroxylated PCBs (OH-PCBs) because they are reported to exhibit relatively high estrogenic activity both in vivo and in vitro. The purpose of this study was to examine the relationship between estrogenicity and carcinogenicity of OH-PCB congeners. The OH-PCBs were tested individually and in combination to determine whether effects of combined OH-PCBs differed from those of these OH-PCBs alone. We evaluated the long-term effects of neonatal exposure to OH-PCBs with treatment doses that were based on the reported binding affinity of specific OH-PCB congeners to estrogen receptor  . BALB/cCrgl female mice were treated within 16 hr after birth by subcutaneous injections every 24 hr, for 5 days. The mice treated with OH-PCB-30 (200 µg/day) or 17β-estradiol (5 µg/day) showed similar increased incidences of cervicovaginal (CV) tract carcinomas (43% and 47%, respectively) . In addition, when mice were treated with OH-PCBs as a mixture, a change in the type of CV tract tumor was observed, shifting from predominantly squamous cell carcinomas to adenosquamous cell carcinoma. From our results, we conclude that the individual OH-PCBs tested were estrogenic and tumorigenic in mice when exposed during development of the reproductive tract. These data support the hypothesis that mixtures may act differently and unexpectedly than do individual compounds. Key words: BALB/cCrgl mouse, estrogenicity, female reproduction, hydroxylated polychlorinated biphenyls, OH-PCBs, tumorigenicity. Environ Health Perspect 113:1022-1026 (2005) . doi:10.1289/ehp.7735 available via http://dx.doi.org/ [Online 20 April 2005]
Address correspondence to J.M. Martinez, National Institute of Environmental Health Sciences, P.O. Box 12233, MD C4-05, Research Triangle Park, NC 27709 USA. Telephone: (919) 541-3466. Fax: (919) 541-4702. E-mail: martine2@niehs.nih.gov We thank J.K. Haseman and G.E. Kissling for their help in all of the statistical analysis. We thank G. Boorman for his confirmation of tumor pathology and R. Newbold and T. Eling for their review of the manuscript. This research was funded by the M.D. Anderson Cancer Center ; the Center of BioEnvironmental Research, Tulane/Xavier University ; and grant 16652 from the National Institute of General Medical Sciences, National Institutes of Health. The authors declare they have no competing financial interests. Received 8 November 2004 ; accepted 20 April 2005. The full version of this article is available for free in HTML or PDF formats. |
