Butler Rondi A, Kelley Melissa L, Olberding Kristen E, Gardner George R, Van Beneden Rebecca J
School of Marine Sciences, University of Maine, Orono, ME 04469-5751, USA.
Comp Biochem Physiol C Toxicol Pharmacol. 2004 Jul;138(3):375-81. doi: 10.1016/j.cca.2004.05.001.
A high prevalence of germinomas has been observed in certain populations of Mya arenaria from eastern Maine. The etiology of these tumors is unknown. We are investigating the hypothesis that exposure to environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) contributes to gonadal carcinogenesis. Clams were exposed to TCDD with or without the initiating compound diethylnitrosamine (DEN) in an attempt to induce germinomas. A TCDD-dependent alteration in gametogenesis was observed in which 32.5+/-6.5% of individuals exhibited undifferentiated gonads. Analyses of AhR and p53 expression were carried out to identify similarities between naturally occurring neoplastic and TCDD (+/-DEN)-altered reproductive tissues. Neoplastic tissues had significantly less p53 protein than matched controls, whereas TCDD-induced undifferentiated samples exhibited no difference in p53 protein levels compared to controls. No gender-specific differences were observed in AhR mRNA, but there were significant differences in protein levels. AhR was undetectable in male gonadal tissue whereas females exhibited a significant positive relationship between AhR protein levels and stage of ovogenesis. Despite exhibiting some morphological similarity, we conclude the TCDD-induced pathology is not a germinoma. We further suggest the change in reproductive tissue is due to inhibition of cell differentiation and/or development by an AhR-independent mechanism.
在缅因州东部的某些砂海螂种群中，已观察到生殖细胞瘤的高发病率。这些肿瘤的病因尚不清楚。我们正在研究一种假说，即接触环境污染物，如2,3,7,8-四氯二苯并对二恶英（TCDD），会导致性腺癌变。将蛤蜊暴露于TCDD，同时或不添加起始化合物二乙基亚硝胺（DEN），试图诱发生殖细胞瘤。观察到TCDD依赖性的配子发生改变，其中32.5±6.5%的个体表现出未分化的性腺。对AhR和p53表达进行分析，以确定自然发生的肿瘤性组织与TCDD（±DEN）改变的生殖组织之间的相似性。肿瘤组织中的p53蛋白明显少于匹配的对照，而TCDD诱导的未分化样本与对照相比，p53蛋白水平没有差异。在AhR mRNA中未观察到性别特异性差异，但在蛋白水平上存在显著差异。在雄性性腺组织中检测不到AhR，而雌性中AhR蛋白水平与卵子发生阶段之间存在显著的正相关。尽管表现出一些形态学上的相似性，但我们得出结论，TCDD诱导的病变不是生殖细胞瘤。我们进一步认为，生殖组织的变化是由于一种不依赖AhR的机制抑制了细胞分化和/或发育。
