Study of human neurovegetative and hematologic effects of environmental low-frequency (50-Hz) electromagnetic fields produced by transformers.

A survey of neurovegetative and hematologic disorders was conducted in a population (n = 13) exposed occupationally to environmental electromagnetic fields; the population was matched with 13 control subjects. The exposed subjects worked at least 8 h/d for 1-5 y in premises located above transformers and high-tension cables, and the subjects were submitted to low-frequency electromagnetic fields (i.e., 50 Hz) of 0.2 microT-6.6 microT. The subjects were matched with respect to socioeconomic category, sex, and age with a control population of subjects that worked in premises outside of the immediate vicinity of transformers or high-tension cables. The exposed population had a significant increase in degree of certain neurovegetative disorders (i.e., physical fatigue, psychical asthenia, lipothymia, decreased libido, melancholy, depressive tendency, and irritability). In addition, the population experienced a significant fall in total lymphocytes and CD4, CD3, and CD2 lymphocytes, as well as a rise in NK cells. Leukopenia and neutropenia were also observed in two persons permanently exposed to doses of 1.2-6.6 microT. The disorders disappeared when exposure stopped, and they reappeared on reexposure.

Alterations of biological parameters in mice chronically exposed to low-frequency (50 Hz) electromagnetic fields.

In an experimental study we measured changes in hematological, biochemical and cortisol parameters in 6-week-old Swiss mice continuously exposed to ELF generated by a transformer station and high current bus bars. Mean daily exposure of 5.0 microT was maintained for 350 days. Hematological parameters were compared to those of control mice (n=12) exposed to a field level lower than 0.1 microT. Serum biochemical parameters (sodium, potassium, chloride, calcium, magnesium, phosphorus, amylase, creatine phosphokinase, and lactate dehydrogenase) were measured after 28 days of exposure and serum cortisol after 90 and 190 days. Granulocyte/macrophage colony-forming cells (GM-CFC) were counted at the end of the 350-day exposure. On day 20, exposed animals showed a significant decrease in leukocyte, erythrocyte, lymphocyte and monocyte counts and in hemoglobin and hematocrit values, while MCV increased. On days 43 and 63 no significant difference was observed in leukocyte and erythrocyte values, as if hemopoiesis had recovered. On day 90, a significant fall in the leukocyte, polynuclear neutrophil and eosinophil counts was observed in the exposed animals. No significant difference was noted in the biochemical parameters studied. On day 190, exposed animals had neutropenia and a decrease in the cortisol value. On day 350, no significant difference in hematological parameters was noted. Individual differences in sensitivity were observed, as 8 mice in the exposed group showed a significant decrease in the leukocyte, polymorphonuclear neutrophil and GM-CFC counts, while in two mice there was a significant increase in these same values compared to those unexposed mice.

T cell lineage involvement in lymphoid blast crisis of chronic myeloid leukemia.

Cytochemical and immunologic analysis of cells obtained from two patients with chronic myeloid leukemia (CML) during blast crisis reveals markers suggestive of an immature lymphoid phenotype. Peripheral blood mononuclear cells from both patients generated spontaneous lymphoblastoid colonies in methylcellulose, a phenomenon observed in T cell acute lymphoblastic leukemias and T cell non-Hodgkin's lymphomas but not in any other type of leukemia. Colonies derived from one patient were composed predominantly of OKT3+ cells (89%), whereas those from the second patient displayed 42% OKT3+ and OKT6+ cells. In the second patient's colonies, each of five mitoses contained the Philadelphia chromosome (Ph1) and two of five displayed the same additional karyotypic abnormalities as the blast crisis cells. Cells obtained from the two patients during remission still gave rise to spontaneous T cell colonies (greater than 85% OKT3+) and Ph1 was detected in 33% and 60% of the metaphases, respectively. However, when colony growth was induced by an interleukin 2-containing conditioned medium, less than 5% of mitoses were Ph1-positive. These data suggest that: (1) the T cell lineage might be involved in CML; (2) a subset of T cells may remain unaffected by the leukemic process, as demonstrated by the virtual absence of Ph1 in induced T cell colonies; and (3) the spontaneous colony assay seems to select for the growth of malignant T cells.

Colony formation in the absence of added growth factors by peripheral blood T-cell colony-forming cells of patients with T-cell malignancies.

Clonogenic cells from peripheral blood of 13/16 patients with T-cell malignancies generated colonies in methylcellulose in absence of added growth factors or mitogenic stimulation. Spontaneous colonies were also obtained from purified cell fractions (E-OKT3- and/or E+ cells) in 73% and 57% of the patients, respectively. No spontaneous colony growth was observed with mononuclear cells of patients with solid tumors, non-T-cell leukemias or normal subjects. Colonies consisted of acid-phosphatase-positive, myeloperoxidase-and PAS-negative lymphoblasts bearing T-cell surface markers. Although the phenotype of pooled colony cells from either unfractionated mononuclear cells or E-OKT3- -derived colonies varied from patient to patient, the colonies, like fresh leukemic cells, were mostly composed of relatively immature cells as assessed by the high proportion (greater than 40%) of OKT6+ and OKT10+ cells and the low proportion (less than 40%) of OKT3+ and/or E+ cells. Cytogenetic analysis of colony cells revealed either normal metaphases or chromosome anomalies similar to those observed in fresh leukemic cells. Moreover, cells from primary colonies exhibited a capacity for self-renewal in the absence of added growth factors.

Heterogeneity of peripheral blood T-cell colony-forming cells in patients with T-cell malignancies.

Some peripheral blood clonogenic T-cells from patients with T-cell malignancies can generate colonies in methylcellulose in the absence of added growth factors or mitogen stimulation (T-CFCs). T-CFC from these patients were also able to form colonies in semi-solid media in the presence of added growth factors (T-CFCi). T-CFCs, in contrast to T-CFCi, were highly clonogenic cells possessing self-renewal capacity in the absence of added growth factors. T-CFCs were in cell cycle and more sensitive to Ara-C or ADM (D10 = 0.009 and 0.025 microgram/ml respectively than T-CFCi (D10 = 1 and 2 micrograms/ml respectively). Furthermore, T-CFCs were more radiosensitive (Do less than 1.1 Gy) than T-CFCi (Do less than 5 Gy). T-cell precursors from patients with immature blast cells (E-, OKT3-, OKT6+, OKT10+) were independent of added growth factors for their in vitro proliferation whereas in cases with mature blast cells (E+, OKT3+) T-CFC were significantly more dependent. These observations strongly suggest that T-CFCs and T-CFCi represent different cell subsets. The phenotype of pooled induced and spontaneous T-cell colonies was highly individualized. However, colonies contained a significant proportion of relatively immature T-cells as assessed by the proportion of OKT6+, OKT10+, OKT3+ and E+ cells. The phenotype of colony cells was quite similar to that observed on fresh leukemic cells suggesting a defect of the in vitro differentiation of both T-CFCs and T-CFCi.