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It has been proposed that extremely low frequency magnetic fields may enhance tumorigenesis through a co-promotional mechanism. This hypothesis has been further tested using the two-stage model of mouse skin carcinogenesis, i.e. 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion of skin carcinogenesis in mice initiated by a single subcarcinogenic dose of 7,12-dimethylbenz[a]anthracene. Experimentation utilized three different doses of TPA within its dose-response range (0.85, 1.70 or 3.40 nmol) and examined the following early biomarkers of tumor promotion after 1, 2 and 5 weeks of promotion: increases in epidermal thickness and the labeling index of epidermal cells, induction of epidermal ornithine decarboxylase activity and down-regulation of epidermal protein kinase C activity. Mice exposed to a 60 Hz magnetic field having a flux density of 2 mT for 6 h/day for 5 days/week were compared with mice exposed to an ambient magnetic field. Within the sensitivity limits of the biomarker methodology and the exposure parameters employed, no consistent, statistically significant effects indicative of promotion or co-promotion by the magnetic field were demonstrated.

Several studies have suggested that exposure to 50 Hz magnetic fields promote chemically induced breast cancer in rats. Groups of 100 female Sprague-Dawley rats were initiated with a single 10 mg gavage dose of 7,12-dimethylbenz[a]anthracene (DMBA) at 50 days of age followed by exposure to ambient fields (sham exposed), 50 Hz magnetic fields at either 1 or 5 Gauss (G) field intensity or 60 Hz fields at 1 G for 18.5 h/day, 7 days/week for 26 weeks. A vehicle control group without DMBA was included. Rats were palpated weekly for the presence of tumors. There was no effect of magnetic field exposure on body weight gains or the time of appearance of mammary tumors. At the end of 26 weeks, the animals were killed and the mammary tumors counted and measured. Mammary gland masses found grossly were examined histologically. The mammary gland carcinoma incidence was 96, 90, 95 and 85% (P < 0.05, decrease) for the DMBA controls, 1 G 50 Hz, 5 G 50 Hz and 1 G 60 Hz groups, respectively. The total numbers of carcinomas were 649, 494 (P < 0.05, decrease), 547 and 433 (P < 0.05, decrease) for the DMBA controls, 1 G 50 Hz, 5 G 50 Hz and 1 G 60 Hz groups, respectively. The number of fibroadenomas varied from 276 to 319, with the lowest number in the 1 G 60 Hz exposure group. Measurement of the tumors revealed no difference in tumor size between groups. In this breast cancer initiation-promotion study in female Sprague-Dawley rats, there was no evidence that 50 or 60 Hz magnetic fields promoted breast cancer under the conditions of this assay. This study does not support the hypothesis that magnetic field exposure can promote breast cancer in this rat model.

Several studies suggest that exposure to 50 Hz magnetic fields may promote chemically induced breast cancer in rats. Groups of 100 female Sprague-Dawley rats were initiated with four weekly 5 mg gavage doses of 7,12-dimethylbenz[a]anthracene (DMBA) starting at 50 days of age. After the first weekly DMBA administration, exposure to ambient fields (sham exposed), 50 Hz magnetic fields at either 1 or 5 G field intensity or 60 Hz fields at 1 G for 18.5 h/day, 7 days/week was initiated. Exposure continued for 13 weeks. A vehicle control group without DMBA was included. In a second study, using lower doses of DMBA, groups of 100 female Sprague-Dawley rats were initiated with four weekly doses of 2 mg of DMBA starting at 50 days of age followed, after the first weekly DMBA administration, by exposure to ambient fields (sham exposed) or 50 Hz magnetic fields at either 1 or 5 G field intensity for 18.5 h/day, 7 days/week for 13 weeks. Rats were weighed and palpated weekly for the presence of tumors. There was no effect of magnetic field exposure on body weight gains or on the time of appearance of mammary tumors in either study. At the end of 13 weeks, the animals were killed and the mammary tumors counted and measured. Mammary gland masses found grossly were examined histologically. In the first 13 week study, the mammary gland carcinoma incidences were 92, 86, 96 and 96% for the DMBA controls, 1 G, 50 Hz, 5 G, 50 Hz and 1 G, 60 Hz groups, respectively. The total numbers of carcinomas were 691, 528 (P < 0. 05, decrease), 561 and 692 for the DMBA controls, 1 G, 50 Hz, 5 G, 50 Hz and 1 G, 60 Hz groups, respectively. In study 2, the mammary gland carcinoma incidences were 43, 48 and 38% for the DMBA controls, 1 G, 50 Hz and 5 G, 50 Hz groups, respectively. The total numbers of carcinomas were 102, 90 and 79 for the DMBA controls, 1 G, 50 Hz and 5 G, 50 Hz groups, respectively. There was no effect of magnetic field exposure on tumor size either by in-life palpation or by measurement at necropsy in either study. There was no evidence that 50 or 60 Hz magnetic fields promoted breast cancer in these studies in female rats. These studies do not support the hypothesis that magnetic field exposure promotes breast cancer in this DMBA rat model.

Labeled zinc incorporation by erythrocytes of diseased or injured animals may reveal zinc-status information when borderline zinc deficiencies exist. The 65Zn uptake by red blood cells of skin-irradiated sheep was much greater than that of cells from control sheep, and factors affecting this uptake were studied. The increased 65Zn uptake was not influenced by the change in packed cell volume, nor could the uptake be altered by extracorporeal irradiation of the red blood cells. The nominal rate of 65Zn uptake during a 10-hr incubation period was .6% per hour for control cells and 1.4% per hour for cells from injured sheep. Hypoalbuminemia and hyperglobulinemia resulted from the irradiation injury, and this change in plasma composition could account for part, but not all, of the differences in uptake between cells from injured and control sheep. Significant differences between the cells from these two sources were still observed when the influence of the plasma was removed. These differences (1) could be due to an increased zinc permeability resulting from injury sustained by the cells as they circulated through injured tissue, or (2) may be associated with the role of zinc in would healing.

Zinc, Cu, Ca, Mg and Fe contents of plasma and/or erythrocytes of 184 kg-steers were studied following exposure of the steers to either (1) whole-body gamma irradiation, (2) beta irradiation of the gastrointestinal tract, (3) beta irradiation of the skin and (4) all combinations of the above. Gastrointestinal (GI) irradiation reduced plasma Zn concentrations 1, 2 and 3 weeks after irradiation, but no detectable change occurred in the erythrocyte concentration of stable Zn. The uptake of 65Zn by erythrocytes from control steers averaged about 5%; whereas the uptakes of the GI- and skin-irradiated steers exceeded 10%. Hypoferremia and hypercupremia accompanied the injury and infection produced by GI and skin irradiation. The decline of plasma Ca and Mg levels following GI irradiation appeared to be the result of radiation induced anorexia, as control animals with a restricted feed intake had a similar reduction in plasma Ca and Mg.

Sprague-Dawley rats were given access to water containing control, 10, or 25 ppm Cd beginning on day 0 of gestation. On day 21 of gestation, fetal and maternal tissues were collected from dams which had been dosed 24 hr previously with 16 μCi of 45CaCl2. Maternal and fetal hematocrits decreased, indicating a possible interference with iron metabolism. No changes in total or radiocalcium found in fetal body were detected as a function of Cd treatment. Fetal bone stable and radiocalcium increased by as much as 33% at 25 ppm while fetal liver and kidney stable Ca decreased compared to controls.It is evident that low Cd exposures lead to changes in fetal Ca metabolism rather than causing changes in the amount of Ca transported across the placenta.

The ontogeny of hepatic metallothioneins (Mt) in fetal tissue as related to dietary and hepatic Zn was investigated. Sixty 6-month-old female rats were divided into two groups and given either double-distilled water or water containing 700 μg of Zn per milliliter. Dams from each group were killed on 16, 19, or 21 days of gestation, and maternal and fetal livers were removed. Mt content of the tissue was estimated by Piotrowski's Hg-saturation method. Results established the presence of an endogenous hepatic Mt in the fetal rat as early as 16 days of gestation. We further demonstrated a marked progressive increase in fetal Mt from Day 16 through gestation accompanied by a decrease in maternal hepatic Mt. It is suggested that Zn increased fetal Mt by inducing fetal synthesis, redistributing fetal Mt, or increasing Mt transport to the fetus, because both fetal and maternal hepatic Mt were increased. Fetal hepatic Mt concentration was several times greater than maternal Mt at corresponding stages of gestation. Mt may serve to either ensure adequate storage of Zn or Cu for fetal development or protect the fetus against metal toxicity, but the significance of these high endogenous levels of fetal Mt are not clear at this time.

The ligated segment technique was used to compare the gastrointestinal absorption of methylmercury and mercury chloride in the rat. Methylmercury was more readily absorbed (15-35 times greater, depending on the absorption site) than inorganic mercury from all ligated segments. The relative order of methylmercury absorption from ligated segments was as follows: duodenum > stomach = ileum > jejunum. Differences in absorption of inorganic mercury between gastrointestinal segments were not observed. Endogenous excretion of both forms of mercury into intestinal tissue were equal. Our data indicate that the absorption of methylmercury from the stomach is significant relative to other parts of the gastrointestinal tract and that the stomach must be considered a major site of absorption.

It has been proposed that extremely low frequency (ELF) magnetic fields may enhance tumorigenesis through a co-promotional mechanism. This hypothesis has been further tested using the two-stage model of mouse skin carcinogenesis, i.e. 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion of skin tumors in mice initiated by a single subcarcinogenic dose of 7,12-dimethylbenz[a]anthracene. Experimentation described herein utilized the SENCAR mouse and examined the effect of a magnetic field on skin tumor promotion induced by three different doses of TPA within its dose-response range, i.e. 0.85, 1.70 or 3.40 nmol, administered twice per week. SENCAR mice (56/treatment group) were exposed to a 60 Hz magnetic field having a flux density of 2 mT for 6 h/day for 5 days/week and compared with mice exposed to the ambient magnetic field. Tumor incidence and multiplicity were monitored weekly for 23 weeks of TPA promotion. Statistical evaluation of the effects of the magnetic field on tumor incidence and multiplicity did not reveal any statistically significant effects; thus, within the sensitivity limits imposed by the animal model and the exposure parameters employed, no promotional or co-promotional effect of a 2 mT magnetic field on skin tumor development in SENCAR mice could be demonstrated.

Associations between exposure to 60-Hz magnetic fields in residential and occupational environments and the incidence of leukemia and other cancers has been suggested by the results of a number of epidemiology studies. To address these potential associations, a study has been conducted to determine if 60-Hz magnetic fields can alter the clinical progression of leukemia. In the large granular lymphocytic (LGL) leukemia model, spleen cells from aged leukemic rats were transplanted into young, male Fischer 344 rats, producing leukemia in a relatively short period. A total of 72 animals were randomly assigned to four treatment groups (18/group) as follows: (1) 10 G; (2) sham exposed (null energized field) (approximately 20 mG); (3) ambient controls (<1 mG); and (4) positive controls (5 Gy whole body irradiation from Cobalt-60, 4 days before initiation of exposure). At the initiation of exposure or sham-exposure, all rats were injected (i.p.) with 2.2x10(7) fresh, viable, LGL leukemia cells. The magnetic fields were activated for 20 h per day, 7 days per week; all exposure conditions were superimposed over the natural ambient magnetic field. Eighteen rats from each treatment were bled at weeks 0, 2, 4, 5, 6, 7, 8 and 10 to monitor, in the same set of animals, the clinical progression of the LGL disease and survival of the animals. Peripheral blood hematological changes were monitored to evaluate the progression of the leukemia. In general, no significant or consistent differences were detected between the magnetic field exposed and the ambient field control groups, although some inconsistent and random differences were occasionally observed. These data indicate that the 10 G magnetic fields did not significantly alter the clinical progression of LGL leukemia in Fischer 344 rats.

Sixteen 28-kg yearling wether lambs were fed 0, 45.7, 68.0, or 92.2 mCi of 90Y-tagged fallout simulant (44–86 mi in diameter) during a 3-day period. The sheep were killed and necropsies performed after 15 days of clinical observation. Anorexia, diarrhea, pyrexia and loss of weight were the most prominent clinical signs. Anorexia appeared to be the most closely correlated early clinical indicator of radiation injury to the gastrointestinal tract: diarrhea and pyrexia were more variable. The most severe radiation damage observed at necropsy was in the ventral compartments of the rumen. Abomasal injury was rather superficial and only minor damage occurred throughout the remaining gastrointestinal tract. Nearly 100 of the ingested sand tagged with tracer 46Sc was excreted by control sheep and sheep consuming the lowest level of 90Y-tagged sand, but the sheep fed 68.0 and 92.2 mCi of 90Y excreted only 82 and 62 of the dose, respectively.