Urogenital carcinoma in California sea lions (Zalophus californianus): Molecular alterations and potential association with environmental contaminants.

摘要

California sea lions have a high prevalence of aggressive urogenital carcinoma The goal of these investigations was to further characterize and identify molecular alterations in sea lion urogenital carcinoma that could be associated with a high environmental contaminant burden.;Reproductive tract histomorphology was described and presence of estrogen receptor alpha (ER alpha) and progesterone receptor (PR) expression evaluated by immunohistochemistry in unaffected sea lions. During large portions of the breeding cycle, ovaries contained corpora lutea (CL) and variably developed follicles. Uterine morphology suggested estrogen influence during the summer pupping and estrus period and throughout the spring. Squamous differentiation of cervical and vaginal epithelium occurred during estrus and in the spring. Both receptors were expressed throughout reproductive tissues with ER alpha expression highest during pupping and estrus and in the spring. Cyclic changes in PR expression were minimal. In males, ER alpha and PR were identified throughout reproductive tissues including the penis and prepuce. In both males and females, ER alpha expression was often more intense in stroma than in epithelium. Results indicate that hormone receptors are expressed throughout male and female reproductive tissues suggesting potential responsiveness to endogenous hormones or chemicals mimicking steroid hormone action.;Expression of ER alpha, PR, p53 and proliferation index were evaluated by immunohistochemistry in sea lions with metastatic carcinoma and intraepithelial (IN) urogenital neoplasia. Estrogen receptor alpha expression decreased in IN compared to normal epithelium and expression in metastatic lesions was absent. Neoplastic cells expressed PR in IN of all grades and in metastatic tumors. Proliferation index and p53 expression increased with lesion grade. Results indicate that endogenous hormones, contaminants that interact with hormone receptors, and altered p53 may play a role in urogenital carcinogenesis.;Lastly, DNA adducts were evaluated as biomarkers of contaminant-induced DNA damage in sea lions with and without urogenital neoplasia and compared to contaminant levels detected in these animals. Hepatic DNA adducts increased with increasing standard length and age, however levels were not different between affected and non-affected animals. Hepatic adducts yielded a specific autoradiogram pattern, which differed from patterns expected from measured contaminants. DNA adducts were infrequent in reproductive tissues.