Differences in phenotypes of normal and malignant cells concerning chromosomal fragility and ganglioside expression

The spontaneous chromosomal fragility was tested by light microscopy observation of metaphases from peripheral blood lymphocytes of 8 patients with malignancies and of 8 healthy controls. In the tested patients, a significantly higher frequency of the spontaneous chromosomal fragility was observed compared to the controls, especially in the centromere chromosomal regions. Of particular interest were interactions involving gangliosides, the reduced form of tri-peptide glutathione (GSH) and/or of tumor-suppressor protein HACE1. The average titers of gangliosides and of anti-ganglioside antibodies in extracts from experimental in vitro models of laboratory-incubated cultures of mouse embryonic 3T3 fibroblasts, of mouse malignant myeloma cells, as well as of mixed cultures of both cellular types, were determined after previous passing of each one through GSH-agarose columns about the “selection” of the molecules in each one of the described samples, possessing affinity to GSH. Additionally, the presence and expression of the tumor-suppressor gene HACE-1 in the genome of mouse embryonic stem cells (mESCs) and malignant human cervical carcinoma HeLa cells, both containing an additional copy of this gene, inserted by transfection with appropriate recombinant DNA vectors containing a copy of the tumor-suppressor gene, were tested. The developed experimental in vitro models show specific intermolecular interactions, which could prevent the disease development. Furthermore, a possibility about the production of antibodies/immunoglobulins by non-lymphoid cellular types was shown. Because the antibodies produced in this manner are outside the germinal centers in the specialized lymphoid tissues and organs, the control of their functions by small ions and molecules, such as gangliosides, is important.