Epidemiological studies conducted on the incidence of cancer correlated to electromagnetic field (EMF) exposure in the home and work environment have designated lymphoma, nervous system tumors and childhood leukemia as the most common types of cancer. In view of the prominent role of human neoplastic B-cells in these cancers, the proposed study seeks to investigate crucial functional and structural aspects of B-cell biology. The long-term objectives of the proposed study include (1) investigating the biochemical basis of EMF exposures typical of home and work environments promoting the incidence of B-cell-related cancers such as lymphomas and leukemias, (2) determination of the role of cell-surface cytokine receptors in the patterns of aberrant growth and non-differentiation characteristic of neoplastic B-cells, and the development of therapeutic methods to counteract these abnormal mechanisms, and (3) examination of 60-Hz (power frequency) fields which may prove to be carcinogenic.
Specific aims i n this proposal include (1) demonstrating whether EMF exposure causes modifications in the proliferation, differentiation and cytokine production of normal and neoplastic B-cells, (2) determining whether under EMF exposure, neoplastic B-cells fail to differentiate because of (a) lack of Interleukin-6 receptors, (b) overexpression of growth factor receptors, and/or (c) lack of an appropriate source of growth and differentiation factors, and (3) observing EMF effects on the human immune system in an in vivo model. The proposed experimental design consists of two stages. First, in vitro studies are conducted under optimized and precisely measured pulsed and continuous EMF exposure patterns. Two different cell types, established human B-cell lines which are growth-factor (BCGF) dependent and normal activated B-cells, are assayed for immunoglobulin secretion and then for receptor-ligand binding with B-cell modulating cytokines. Both cell types have membrane comparability with regard to growth factor surface receptors. Second, these in vitro results are correlated and confirmed by reconstituting a quasi-functional human immune system in severe combined immunodeficiency (SCID) mice, an in vivo model which will be subjected to varying EMF exposure patterns and characterized for the growth and differentiation factor genes, that include IL2, BCGF, and IL6 and their proteins.
| Amato, S F; Swart, J M; Berg, M et al. (1998) Transient stimulation of the c-Jun-NH2-terminal kinase/activator protein 1 pathway and inhibition of extracellular signal-regulated kinase are early effects in paclitaxel-mediated apoptosis in human B lymphoblasts. Cancer Res 58:241-7 |
| Mehta, S; Blackinton, D; Manfredi, M et al. (1997) Taxol pretreatment of tumor targets amplifies natural killer cell mediated lysis. Leuk Lymphoma 26:67-76 |
