Aryl hydrocarbon receptor (AhR)-independent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on softshell clam (Mya arenaria) reproductive tissue.

ABSTRACT

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.