BACKGROUND: Endocrine-disrupting chemicals have been shown to have broad effects on development, but their mutagenic actions that can lead to cancer have been less clearly demonstrated. Physiological levels of estrogen have been shown to stimulate DNA damage in breast epithelial cells through mechanisms mediated by estrogen-receptor alpha (ERa). Benzophenone-3 (BP-3) and propylparaben (PP) are xenoestrogens found in the urine of >96% of U.S. population. OBJECTIVES: We investigated the effect of BP-3 and PP on estrogen receptor-dependent transactivation and DNA damage at concentrations relevant to exposures in humans. METHODS: In human breast epithelial cells, DNA damage following treatment with 17b-estradiol (E 2), BP-3, and PP was determined by immunostaining with antibodies against c-H2AX and 53BP1. Estrogenic responses were determined using luciferase reporter assays and gene expression. Formation of R-loops was determined with DNA: RNA hybrid-specific S9.6 antibody. Short-term exposure to the chemicals was also studied in ovariectomized mice. Immunostaining of mouse mammary epithelium was performed to quantify R-loops and DNA damage in vivo. RESULTS: Concentrations of 1 lM and 5 lM BP-3 or PP increased DNA damage similar to that of E 2 treatment in a ERa-dependent manner. However, BP-3 and PP had limited transactivation of target genes at 1 lM and 5 lM concentrations. BP-3 and PP exposure caused R-loop formation in a normal human breast epithelial cell line when ERa was introduced. R-loops and DNA damage were also detected in mammary epithelial cells of mice treated with BP-3 and PP. CONCLUSIONS: Acute exposure to xenoestrogens (PP and BP-3) in mice induce DNA damage mediated by formation of ERa-dependent R-loops at concentrations 10-fold lower than those required for transactivation. Exposure to these xenoestrogens may cause deleterious estrogenic responses, such as DNA damage, in susceptible individuals.
From 1951 to 1976 234 patients with invasive carcinoma of the vulva were treated at the Department of Obstetrics and Gynaecology, Medical School Hannover. 53.3% of these patients underwent simple vulvectomy. Radical vulvectomy and lymphadenectomy was performed in 17.9%. 45.7% received postoperative radiotherapy. -213 patients were followed up 5 years or more. After surgery alone the 5-year-survival rate was 56.9%, after operation and radiotherapy 43.4%, after exclusive radiation 14.2%. The 5-year-survival rate of all patients was 42.7%.
The controvery about the increase of carcinoma of the endometrium following estrogen therapy led to an investigation of the correlation between estrogen and cancer of the breast because of the close link between carcinoma of the endometrium and carcinoma of the breast. In the statistical matched pair comparison 120 cases of carcinoma of the breast were compared with thoroughly selected controls. To each patient with carcinoma of the breast a control person with essentially the same risk factors was assigned. It was found that: 1) Estrogen therapy in general does not lead to an increased risk for carcinoma of the breast. 2) The separate evaluation of different estrogen preparations showed no increase of the risk. 3) The risk was not increased by prolonged treatment with estrogen. 4) The number of patients taking conjugated estrogens was higher in the control group than in the carcinoma group. 5) The coincidence of estrogen treatment with the other risk factors of nulligravity, hypertension and obesity did not result in an increased risk for carcinoma of the breast.
A case of dysgerminoma of the ovary in a 36-year-old woman in her 10th week of gestation is reported. Hysterectomy, bilateral adnectomy and omentectomy was performed followed by radiation therapy of the pelvis and paraaortic region. Until now only about 60 cases of ovarian dysgerminoma during pregnancy have been described in literature. The tumour was rarely detected within the first trimester. In these cases the safety of the patient should rank higher than the pregnancy itself.
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