Adult male and female B6C3F1 mice were exposed to perfluorooctane sulfonate (PFOS) daily via gavage for 28 days (0, 0.005, 0.05, 0.1, 0.5, 1, or 5 mg/kg total administered dose [TAD]). Following exposure, various immune parameters were assessed and serum PFOS concentrations were determined. Lymphocyte proliferation was not altered in either gender. Natural killer cell activity was increased compared with control at 0.5, 1, and 5 mg/kg TAD in male mice but was not altered in female mice. At these treatment levels, splenic T-cell immunophenotypes were minimally altered in females, but all T-cell subpopulations were significantly modulated in males beginning at 0.1 mg/kg TAD. The sheep red blood cell (SRBC) plaque-forming cell (PFC) response was suppressed in male mice beginning at 0.05 mg/kg TAD and in females at 0.5 mg/kg TAD. Serum trinitrophenyl (TNP)-specific IgM titers were also decreased by PFOS after TNP-LPS (TNP conjugated to lipopolysacharide) challenge suggesting that the humoral immune effects may be attributed to the B-cell rather than T-cell because both T-dependent (SRBC) and T-independent (TI) (TNP-LPS) antigens result in suppressed IgM production. Based on the PFC response, the low observed effect level (LOEL) for males was 0.05 mg/kg TAD (ED(50) = 0.021 mg/kg TAD) and for females was 0.5 mg/kg TAD (ED(50) = 0.59 mg/kg TAD). Measured PFOS serum concentrations at these dose levels were 91.5 +/- 22.2 ng/g and 666 +/- 108 ng/g (mean +/- SD), respectively. The male LOEL serum level was approximately 14-fold lower than reported mean blood levels from occupationally exposed humans and fell in the upper range of concentrations reported for the general population. Overall, this study provides a profile of PFOS immunotoxicity showing effects at levels reported in humans and identifies the B-cells as a potential target.

Methylation of the RAR-beta2 gene may be an initial step in breast carcinogenesis; treatment of cancer patients with demethylating agents followed by retinoic acid may offer a new therapeutic modality.

Gene silencing through de novo methylation of CpG island promoters contributes to cancer. We find that Mbd2, which recruits co-repressor complexes to methylated DNA, is essential for efficient tumorigenesis in the mouse intestine. As Mbd2-deficient mice are viable and fertile, their resistance to intestinal cancer may be of therapeutic relevance.

In the past, several authors described an association of vitiligo with autoimmune disorders and the presence of different tissue autoantibodies. A review of the literature showed large differences in the results. Therefore, 321 patients with vitiligo (male/female ratio 114/207) were examined to see whether the frequencies of associated diseases and phenomena (i.e. Koebner phenomenon, canities praecox, halo nevi, poliosis circumscripta), the number of pigmented lesions and the presence of autoantibodies are of significance in order to support (a) a subentity of childhood vitiligo and (b) whether there is a true predisposition or association of autoimmune or other diseases in this group of patients. The data confirm earlier results of a prevalence of thyroid disease and the presence of thyroid antibodies, whereas other diseases are a random event. 6.2% of the patients had congenital nevi compared with 2.8% in a normal healthy population. Based on the results of this study and the significant higher risk for development of melanomas in this patient group, an annual checkup is recommended.