Martinez Jeanelle M, Stephens L Clifton, Jones Lovell A
Department of Gynecologic Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA.
Environ Health Perspect. 2005 Aug;113(8):1022-6. doi: 10.1289/ehp.7735.
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.
新生小鼠模型一直是确定哺乳动物早期接触雌激素类物质的长期影响的重要工具。利用该模型，我们比较了2',4',6'-三氯-4-联苯酚（OH-PCB-30）和2',3',4',5'-四氯-4-联苯酚（OH-PCB-61）作为典型雌激素性羟基化多氯联苯（OH-PCBs）的影响，因为据报道它们在体内和体外均表现出相对较高的雌激素活性。本研究的目的是检验OH-PCB同系物的雌激素性与致癌性之间的关系。分别对OH-PCBs进行单独和联合测试，以确定联合使用OH-PCBs的效果是否与单独使用这些OH-PCBs的效果不同。我们根据特定OH-PCB同系物与雌激素受体α的报道结合亲和力，用治疗剂量评估了新生小鼠接触OH-PCBs的长期影响。BALB/cCrgl雌性小鼠在出生后16小时内每24小时皮下注射一次，共注射5天。用OH-PCB-30（200微克/天）或17β-雌二醇（5微克/天）处理的小鼠宫颈阴道（CV）道癌的发生率相似地增加（分别为43%和47%）。此外，当小鼠用OH-PCBs混合物处理时，观察到CV道肿瘤类型发生变化，从主要的鳞状细胞癌转变为腺鳞癌。从我们的结果来看，我们得出结论，在生殖道发育期间接触时，所测试的单个OH-PCBs在小鼠中具有雌激素性和致瘤性。这些数据支持了这样一种假设，即混合物的作用可能与单个化合物不同且出乎意料。
