Lina Xing

Peking University, Beijing, Beijing Shi, China

Are you Lina Xing?

Claim your profile

Publications (6)18.6 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The potential developmental toxicity of environmental estrogenic endocrine disruptors have become a great concern in recent years. In this study, two typical environmental oestrogen, namely, bisphenol A (BPA) and genistein (GEN) were investigated for potential embryotoxicity using the embryonic stem cell test model. Afterwards, a 4×4 full factorial design and the estimated marginal means plot were performed to assess the combined effects of these two compounds. According to the linear discriminant functions and classification criteria, bisphenol A and genistein were classified as weakly embryotoxic and strongly embryotoxic respectively. As for combined effects, the overall interaction between BPA and GEN on embryonic stem cells (ESCs) differentiation was synergistic at low dosages, however, on ESCs and 3T3 cell proliferation, the predominate action was additive. Considering the actual daily intake of these chemicals, it is concluded that BPA alone might not have adverse reproductive or developmental effects on human being. However, given that BPA and GEN do have synergistic effect at low concentration, they may disturb normal embryo development together, which could result in birth defect and behavioral alterations later in life.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 08/2013; · 2.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Bisphenol A (BPA) has been widely used in the manufacture of polycarbonate plastic, water bottles and food containers. Previous studies have established that BPA could cause developmental toxicity by inhibiting the proliferation and differentiation of rat embryonic midbrain (MB) cells in vitro. However, the underlying mechanisms have not been well studied yet. In the current study, we examined the proliferation and differentiation of MB cells treated with 10(-12)-10(-4) M BPA and found that only 10(-4) M BPA inhibited proliferation and differentiation. Then, we investigated the cell cycle progression and apoptosis of MB cells; 10(-4) M BPA caused an explicit S phase and G2/M phase arrest in the cell cycle and increased the percentage of apoptotic cells. Moreover, the phosphorylation of mitogen-activated protein kinase (MAPK) and cyclic-AMP response binding protein (CREB) and the expression of some apoptotic regulatory genes were investigated. BPA (10(-4) M) reduced the phosphorylation of C-Jun N-terminal kinase (JNK) and CREB, and increased the mRNA expression level of Bax and p53. Our findings demonstrated that BPA could cause developmental toxicity through anti-proliferation and pro-apoptosis in MB cells. Multiple signaling pathways, such as the JNK, CREB and p53- mitochondrial apoptosis pathways, participate in these effects.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 11/2012; · 2.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Genistein (GEN) is one kind of phytoestrogen. Several studies have demonstrated the teratogenic potential of GEN in vitro by postimplantation rat whole embryo culture (WEC) assay, but GEN showed no teratogenic effects in vivo even at a dose up to 1000 mg/kg bw/day. The mechanism of such discrepancy is still unclear. Because more than 80% of total genistein (free plus glycoside form) in circulation is its glycoside metabolite, genistin (GIN), we thus hypothesize that genistin is non-teratogenic. To prove this hypothesis, rat whole embryo culture (WEC) and limbud micromass culture methods were applied to compare the teratogenic effects of GEN and GIN on developing embryos in vitro. In WEC assay, we found that the development of embryos was affected by GEN treatment dose-dependently, while GIN-treated embryos displayed slight developmental defects only at the highest dose (222 μM). In micromass culture assay, the IC50 of cell proliferation and differentiation for GEN were 15.6 and 37.2 μM, respectively, while neither was influenced by GIN treatment up to 111 μM. Collectively, our study indicated that GEN showed no teratogenic effects in vivo probably due to its transformation to the non-teratogenic metabolite, GIN.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 05/2012; 50(8):2831-6. · 2.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Bisphenol A (BPA), widely used in industry and dentistry, and genistein (GEN), the predominant component of soy product, are both known environmental estrogen. In the present study, we investigated the developmental toxicity of BPA and GEN and their combined effect using micromass test, which is one of three standard alternative developmental toxicity tests recommended by European Center for the Validation of Alternative Methods (ECVAM). The results showed that IC50-P (cell proliferation) and IC50-D (cell differentiation) of BPA and GEN were approximately 20 and 5 μg/ml, respectively. No observed adverse effect level (NOAEL) of BPA and GEN were 10 and 0.94 μg/ml, respectively. The manifestation of BPA as a teratogen was insufficient, although the "low dose" effect should be paid attention to. While the evidence of GEN as a teratogen was solid, especially with the consideration of "high dose" application in clinical treatment. The combined effect of BPA and GEN was generally additive action except that in MB proliferation.
    Toxicology in Vitro 10/2010; 25(1):153-9. · 2.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The potential teratogenic effects and fetal toxicity of environmental estrogenic endocrine disruptors have become a great concern in recent years, and they have yet to be fully characterized. In the present study, the teratogenic effects of bisphenol A (BPA) and genistein (GEN) on rat embryos during their critical period of organogenesis were investigated using a whole-embryo culture experiment. The combined exposure effects of BPA and GEN were explored using a 4 x 4 full factorial design. Both BPA and GEN produced concentration-dependent inhibition of embryonic development, beginning at 32.0 and 10.0 microg/ml, respectively. Full factorial and isobologram analyses revealed a significant synergistic interaction between BPA and GEN for most end points (12 out of 20 tested), as indicated by the enhanced developmental toxicity of BPA after coexposure with different dose levels of GEN. In particular, serious malformations and a higher abnormal frequency of the central nervous system were induced by the combination of BPA and GEN. Our findings suggest that GEN may be embryotoxic and teratogenic to humans. BPA alone may not be a potential teratogen, but these two estrogenic chemicals have a synergistic effect on embryonic development when present together during the critical period of major organ formation. The current findings suggest that pregnant women should not take soy supplements, but more studies are necessary to provide a conclusive recommendation.
    Toxicological Sciences 03/2010; 115(2):577-88. · 4.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Some studies show that Cd(2+) and Hg(2+) may induce cell proliferation and apoptosis via biphasic dose-response relationship in human cells. However, mechanisms underlying this phenomenon are still in puzzle. In this study, we aim at detecting the biphasic effects of Cd(2+) and Hg(2+) on proliferation and apoptosis of human embryonic kidney 293 (HEK293) cells, analyzing the change of the mitogen-activated protein kinase (MAPK) pathways, and discussing the relationship between them. The results demonstrate that Cd(2+) and Hg(2+) can stimulate cell proliferation at lower concentrations (0.05 and 0.5 microM) but inhibit it at higher concentrations (50 and 500 microM). Apoptosis increases at higher concentrations (50 and 500 microM) of Cd(2+) and Hg(2+). While 0.5 microM Cd(2+) and Hg(2+) decrease the JNK phosphorylation, 50 microM Cd(2+) and Hg(2+) increase the JNK and P38 phosphorylation. When HEK293 cells are treated with 20 microM JNK inhibitor or 100 microM ERK1/2 inhibitor, the cell proliferation do not increase significantly at low concentrations (0.05 and 0.5 microM), but still decrease at high concentrations (50 and 500 microM). When HEK293 cells are treated with 20 microM P38 inhibitor, the tendency of cell proliferation is not affected. Data in our study suggests that activation of MAPK pathway may be involved in the biphasic effect induced by Cd(2+) and Hg(2+).
    Toxicology in Vitro 04/2009; 23(4):660-6. · 2.65 Impact Factor