Iron-radiofrequency synergism in lymphomagenesis.

The parenteral iron administration effects on the acceleration of lymphomagenesis by radiofrequency exposure were investigated using an animal model that develops spontaneous lymphomas with ageing. Complementary studies of the in vivo uptake of 59Fe-labeled ferric gluconate and ferric-ATP complex showed differences ob absorption and excretion between both iron compounds. In vitro assays of their effects on calcium cellular uptake using a cell model and tissues homogenates showed a molecular structure-dependence. The current results (mortality, clinical and histopathological examinations) demonstrated a synergism between radiofrequency and ferric gluconate, and the increased risk of radiofrequency exposure when it is simultaneous to parenteral iron administration.

Evaluation of health risks caused by radio frequency accelerated carcinogenesis: the importance of processes driven by the calcium ion signal.

The acceleration of carcinogenesis, which was induced either by radio frequency radiation from a cellular telephone or by the ferric-ATP complex, was similar in a mouse strain characterized by age-determined carcinogenesis of lymphoid tissues. Organ hypertrophy, the presence of lymphoid blood and ascites, the development of solid tumours, and mortality were very different to those found in control animals. These results emphasize the role of calcium ion signal influx in the activation of oncogenes and the failure of thymus-determined immune defences.

Role of iron-ATP complex in lymphocyte proliferation and infiltration.

The roles of sodium-ATP (NaATP) and ferric-ATP complex (FeATP) on the proliferation and infiltration of lymphocytes have been studied by evaluation of the hypertrophy and histopathologic examination of spleen and liver, as well of the modifications in the elemental balance of iron, calcium, magnesium, and phosphorus. The results showed that in the implicated biochemical processes, calcium and magnesium have a principal role. An in vitro study on a cell model has permited one to evaluate the effects of deferoxamine, a known iron chelator and inhibitor of human lymphocyte proliferation, on FeATP-modified cellular calcium fluxes. These findings showing a reduced 45Ca2+ uptake in the presence of deferoxamine appear to indicate that in vivo the chelation of blood-borne iron by ATP might play a key role in proliferation and infiltration of lymphocytes, leading to lymphoma development.

Molecular exchange of metal ions and tissular calcium overload.

In vitro and in vivo, mouse tissues assayed for 45Ca2+ uptake have shown that ATP increases the Ca2+ take-up in the presence of lactates of iron and aluminum, but this effect is absent with the citrates. The in vitro metal ion exchange with ATP has been demonstrated by electrophoresis and by chromatography. It is considered the cause of the increased capacity of ATP to modify the cellular effects of lactates. The in vitro modifications of Ca2+ uptake by lactates when in the presence of ATP are much more important than those of citrate. In general, aluminum compounds show a higher Ca2+ uptake and, coincidentally, they have shown a higher carcinogenic capacity than iron ATP.

Toxic and carcinogenic effects of parenteral and percutaneous ATP and its iron complex.

The long term effects of percutaneous, subcutaneous and intraperitoneal administration of sodium-ATP (NaATP) and ferric iron-ATP (FeATP) were studied on an animal model. Both compounds induce a generalized lymphoadenitis which in the case of FeATP led to lymphomas. The analytical study of the involved target tissues showed intracellular composition changes that result from the impairment of the cell membrane permeability. The morbidity and mortality rate were higher with FeATP which seems to be the result of two different, in intensity and duration, interactions with the cell plasma membrane. The influence of the changes in cellular calcium homeostasis, and its relationship with carcinogenesis and immuno response are discussed.

Cellular calcium homeostasis changes in lymphoma-induction by ATP iron complex.

An in vivo comparative study of 45Ca-uptake and lipid peroxidation in tissues of mice treated with ATP complex of iron and sodium salt of ATP shows that only the iron complex produces a sustained increase of intracellular calcium on the organs susceptibles to develop lymphomas. A paralled study of 59Fe-uptake from 59Fe-iron complex of ATP presents a coincidental increase of iron uptake in those organs. To prove the involvement of the calcium homeostasis change in lymphoma-induction we have studied it with the lanthanum complex of ATP. Lanthanum is a well known cellular calcium entry modifier. Based on the results, the increased and sustained entry of extracellular calcium ion appears as the cause of lymphoma-induction by the iron complex. The effects of the calcium-overload in proliferation and neoplastic transformation of lymphocytes, as well as in reducing the immuno-response induced by thymus is discussed.