boron and Cell-Transformation--Neoplastic

WHO has presented a health-based guideline value for boron in drinking water. That fact indicates that a high level of boron is toxic for humans. However, there is no direct evidence of boron-mediated malignant transformation. In this study, human lung epithelial nontumorigenic BEAS-2B cells and tumorigenic A549 cells were used to investigate the tumorigenic toxicity of boron in vitro. Anchorage-independent growth, a hallmark of malignant transformation, was increased by boron at concentrations of 50, 250 and 500 μM in BEAS-2B cells, though the same concentrations of boron had no influence on anchorage-independent growth of A549 cells. Moreover, boron at concentrations of 250 and 500 μM activated the c-SRC/PI3K/AKT pathway of BEAS-2B cells. The results of our in vitro study suggest that exposure to high levels of boron promotes transforming activity of nontumorigenic cells.

Topics: Boron; Cell Line; Cell Transformation, Neoplastic; Epithelial Cells; Humans; Phosphatidylinositol 3-Kinases

Folic acid (FA) has high affinity for the folate receptor (FR), which is limited expressed in normal human tissues, but over-expressed in several tumor cells, including glioblastoma cells. In the present work, a novel pteroyl-closo-dodecaborate conjugate (PBC) was developed, in which the pteroyl group interacts with FR, and the efficacy of boron neutron capture therapy (BNCT) using PBC was investigated. Thus, in vitro and in vivo studies were performed using F98 rat glioma cells and F98 glioma-bearing rats. For the in vivo study, boronophenylalanine (BPA) was intravenously administered, while PBC was administered by convection-enhanced delivery (CED)-a method for direct local drug infusion into the brain of rats. Furthermore, a combination of PBC administered by CED and BPA administered by intravenous (i.v.) injection was also investigated. In the biodistribution experiment, PBC administration at 6 h after CED termination showed the highest cellular boron concentrations (64.6 ± 29.6 µg B/g). Median survival time (MST) of untreated controls was 23.0 days (range 21-24 days). MST of rats administered PBC (CED) followed by neutron irradiation was 31 days (range 26-36 days), which was similar to that of rats administered i.v. BPA (30 days; range 25-37 days). Moreover, the combination group [PBC (CED) and i.v. BPA] showed the longest MST (38 days; range 28-40 days). It is concluded that a significant MST increase was noted in the survival time of the combination group of PBC (CED) and i.v. BPA compared to that in the single-boron agent groups. These findings suggest that the combination use of PBC (CED) has additional effects.

Topics: Animals; Boron; Boron Compounds; Boron Neutron Capture Therapy; Cell Line, Tumor; Cell Transformation, Neoplastic; Folate Receptors, GPI-Anchored; Glioma; Humans; Male; Molecular Targeted Therapy; Rats; Tissue Distribution

Epidemiologic data in volcanic areas suggest that environmental factors might be involved in the increase of thyroid cancer (TC) incidence. Recent reports indicate that several heavy metals and metalloids are increased in volcanic areas. This study aims to evaluate the combined effect of three of these elements Boron (B), Cadmium (Cd), and Molybdenum (Mo) - all increased in the volcanic area of Mt. Etna, in Italy - on thyroid tumorigenesis in the rat.. Female Wistar rats prone to develop thyroid tumors by low-iodine diet and methimazole treatment received ad libitum drinking water supplemented with B, Cd, and Mo at concentrations in the range found in the urine samples of residents of the volcanic area. At 5 and 10 months animals were euthanized, and their thyroid analysed. Statistical analysis was performed with a 2-way unpaired t-test.. No toxic effect of the three elements on the growth of the animals was observed. A significant increase of histological features of transformation was observed in thyroid follicular cells of rats treated with B, Cd, and Mo compared with those of control group. These abnormalities were associated with decreased iodine content in the thyroid.. This study provides the evidence that slightly increased environmental concentrations of B, Cd, and Mo can accelerate the appearance of transformation marks in the thyroid gland of hypothyroid rats.

Topics: Animals; Boron; Cadmium; Cell Transformation, Neoplastic; Female; Molybdenum; Rats; Rats, Wistar; Thyroid Neoplasms