Bisphenol A prevents MCF-7 breast cell apoptosis via the inhibition of progesterone receptor transactivation.

2,2-Bis(4-hydroxyphenyl)propane (bisphenol A; BPA) is an environmental endocrine-disrupting chemical. It mimics the effects of estrogen at multiple levels by activating estrogen receptors (ERs); however, BPA also affects the proliferation of human breast cancer cells independent of ERs. Although BPA inhibits progesterone (P4) signaling, the toxicological significance of its effects remain unknown. Tripartite motif-containing 22 (TRIM22) has been identified as a P4-responsive and apoptosis-related gene. Nevertheless, it has not yet been established whether exogenous chemicals change TRIM22 gene levels. Therefore, the present study investigated the effects of BPA on P4 signaling and TRIM22 and TP53 expression in human breast carcinoma MCF-7 cells. In MCF-7 cells incubated with various concentrations of P4, TRIM22 messenger RNA (mRNA) levels increased in a dose-dependent manner. P4 induced apoptosis and decreased viability in MCF-7 cells. The knockdown of TRIM22 abolished P4-induced decreases in cell viability and P4-induced apoptosis. P4 increased TP53 mRNA expression and p53 knockdown decrease the basal level of TRIM22 and P4 increased TRIM22 mRNA expression independent of p53 expression. BPA attenuated P4-induced increases in the ratio of cell apoptosis in a concentration-dependent manner, and the P4-induced decreases in cell viability was abolished in the presence of 100 nM and higher BPA concentrations. Furthermore, BPA inhibited P4-induced TRIM22 and TP53 expression. In conclusion, BPA inhibited P4-induced apoptosis in MCF-7 cells via the inhibition of P4 receptor transactivation. TRIM22 gene has potential as a biomarker for investigating the disruption of P4 signaling by chemicals.

Decamethylcyclopentasiloxane affects estradiol production in female rats but not H295R cells.

Sex hormones, such as androgens and estrogens, are predominantly produced in the gonads (ovaries and testes) and adrenal cortex. Endocrine-disrupting chemicals (EDCs) are substances that mimic, block, or interfere with hormones in the endocrine systems of humans and organisms. EDCs mainly act via nuclear receptors and steroidogenesis-related enzymes. In the OECD conceptual framework for testing and assessment of EDCs, several well-known assays are used to identify the potential disruption of nuclear receptors both in vivo and in vitro, whereas the H295R steroidogenesis assay is the only assay that detects the disruption of steroidogenesis. Forskolin and prochloraz are often used as positive controls in the H295R steroidogenesis assay. Decamethylcyclopentasiloxane (D5) was suspected one of EDCs, but the effects of D5 on steroidogenesis remain unclear. To establish a short-term in vivo screening method that detects the disruption of steroidogenesis, rats in the present study were fed a diet containing forskolin, prochloraz, or D5 for 14 days. Forskolin increased plasma levels of 17ß-estradiol (E2) and testosterone as well as the mRNA level of Cyp19 in both the adrenal glands and ovaries. Prochloraz induced the loss of cyclicity in the sexual cycle and decreased plasma levels of E2 and testosterone. D5 increased E2 levels and shortened the estrous cycle in a dose-dependent manner; however, potential endocrine disruption was not detected in the H295R steroidogenesis assay. These results demonstrate the importance of comprehensively assessing the endocrine-disrupting effects of chemicals on steroidogenesis in vivo.

[Lineage switch on recurrence from minimally differentiated acute leukemia (M0) to acute megakaryocytic leukemia (M7)].

Phenotypic switch in acute leukemia is a rare phenomenon. We report on a female infant with minimally differentiated acute leukemia (M 0) which underwent a lineage switch on relapse. In March 1997, a 1-year-8-month old girl was admitted to our hospital with a high-grade fever and generalized purpura. Bone marrow showed 84% blasts. The blasts were negative for peroxidase, periodic acid-Schiff and alpha-naphthyl butyrate esterase. Immunophenotypic analyses of the blast cells were positive for CD 13, CD 33 antigens, as well as CD 34. Lymphoid markers all were negative. Though some blasts morphologically demonstrated cytoplasmic blebs, CD 41 was negative and ultrastructural platelet peroxidase was absent. Based on these hematological features, the patient was diagnosed as having AML-M 0. She was treated according to the Children's Cancer and Leukemia Study Group schedule and a complete remission was achieved 1.5 months after starting induction therapy. However, she relapsed in spite of continued chemotherapy in July 1997, when the cytomorphological pattern changed and the patient was diagnosed both morphologically and immunologically as having M 7. Electron microscopy revealed platelet peroxidase (+) and CD 41 (+). Cytogenetic studies on relapse demonstrated inv(3) (q 21 p 25). We attempted aggressive reinduction therapy, but without effect. The patient simultaneously developed severe pneumonia and died in February, 1998. A lineage switch on relapse and resistance to chemotherapy may be associated with the occurrence of genetic aberration.