The effects of dietary administration of 1H, 1H, 2H, 2H-perfluorodecanol (8-2 telomer alcohol), on peroxisome proliferation in the liver of mice were studied. Male ddY mice were fed on a diet containing 8-2 telomer alcohol at concentrations of 0, 0.025, 0.05, 0.1, and 0.2% (w/w) for 7, 14, 21, and 28 days. These treatments with 8-2 telomer alcohol caused liver enlargement in a dose- and duration-dependent manner. Peroxisome proliferation in the liver of mice was confirmed by electron microscopic examination. Peroxisomal acyl-CoA oxidase was induced by these treatments with 8-2 telomer alcohol in a dose- and time-dependent manner. The concentration of perfluorooctanoic acid (PFOA) and related compounds were determined in the liver and plasma, since PFOA had been shown to be a possible metabolite of 8-2 telomer alcohol and to cause significant peroxisome proliferation in rodents. Five metabolites, namely, perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), 2H, 2H-perfluorodecanoic acid (8-2 telomer acid), and two unidentified metabolites, were present in the liver and serum. PFOA was confirmed to be accumulated in the liver of mice following the administration of 8-2 telomer alcohol in a dose- and duration-dependent manner. A linear relationship was observed between the concentration of PFOA and the activity of peroxisomal acyl-CoA oxidase in the liver of mice. These results strongly suggest that PFOA, but not 8-2 telomer alcohol itself, caused peroxisome proliferation in the liver. The present study provided evidence that 8-2 telomer alcohol is converted into PFOA in vivo and that the PFOA formed produces biological effects in the liver of mice.

No abstract

The mechanism that regulates growth in ovarian clear cell adenocarcinoma (CCA) is not well understood. A high incidence of concurrent endometriosis with CCA may indicate that estrogen is a growth promotor in CCA. To determine estrogen as a growth promotor, the authors investigated the presence or absence of estrogen receptor-alpha (ER-alpha), ER-beta, progesterone receptor, and dioxin receptor (i.e., aromatic hydrocarbon receptor) in clinically resected ovarian CCA, serous adenocarcinoma (SAC), endometrioid adenocarcinoma (EAC), and mucinous adenocarcinoma (MAC) specimens using an immunohistochemical method. Expression of ER-alpha and ER-beta messenger ribonucleic acid was examined by reverse transcription-polymerase chain reaction in three established CCA cell lines: KK, RMG-1, and HAC-II. None of the surgically resected CCA and CCA cell lines showed positive staining for ER-alpha. Conversely, 97.2% of SACs, 100% of EACs, and 70% of MACs showed positive nuclear staining for ER-alpha (p < 0.001). Conversely, positive ER-beta staining for CCA (39.3%) was similar to that of SAC (41.7%) and MAC (30.0%). EAC (75%) showed a higher expression of ER-beta (p < 0.02). Progesterone receptor was detected in only 10.7% of CCA, compared with SAC and EAC (SAC, 86.1%; EAC, 91.7%; p < 0.01). Aromatic hydrocarbon receptor was detected in all histologic types at an incidence of approximately 50% to 60%. Messenger ribonucleic acid of ER-alpha and ER-beta was not detected in the three CCA cell lines. These findings indicate biologic characteristics that distinguish CCA from other types of ovarian epithelial cancer.