Long-term effects of neonatal exposure to hydroxylated polychlorinated biphenyls in the BALB/cCrgl mouse.
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 alpha. 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 microg/day) or 17beta-estradiol (5 microg/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.
Martinez
Jeanelle M
JM
Department of Gynecologic Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA. martine2@niehs.nih.gov
Stephens
L Clifton
LC
Jones
Lovell A
LA
D000818:Animals; D000831:Animals, Newborn; D018196:Carcinoma, Adenosquamous / Q000139:chemically induced*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced*; D004785:Environmental Pollutants / Q000633:toxicity; D005260:Female; D006900:Hydroxylation; D051379:Mice; D008807:Mice, Inbred BALB C; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D002583:Uterine Cervical Neoplasms / Q000139:chemically induced*; D014625:Vaginal Neoplasms / Q000139:chemically induced*
D004785:Environmental Pollutants; D011078:Polychlorinated Biphenyls