Fluctuations in Fe, Cu, Zn, Br, As, Se, and Rb concentrations in C57L/J mice bearing BW7756 murine hepatoma using radioisotope-induced X-ray fluorescence.

The effects of selenite or selenate supplementation on the concentration and distribution of Fe, Cu, Zn, As, Br, and Rb are investigated using the radioisotope-induced X-ray fluorescence, RIXRF. These effects are studied in the animals bearing BW7756 murine hepatoma and healthy animals for both of the oxidation states. Selenite and selenate induce different effects on the distribution of selenium, zinc, copper, bromine, and rubidium. The differences may be attributed to the differences in the inter element interaction after absorption into the bloodstream as well as to the mode of their intestinal absorption. Simultaneous supplementation of copper with selenite or selenate at the described levels has a profound influence on the concentration levels of other elements in the normal as well as in the diseased mice. The administration of selenium (0.67 micrograms/g body wt sodium selenite or sodium selenate, daily) and selenium and copper (0.67 and 1.35 micrograms/g body wt, respectively) has no effect on the incidence rate of hepatoma development.

[75Se]selenite and [75Se]selenate fluctuations during the development of murine hepatoma.

The distribution of selenate and selenite selenium in C57L/J mice during the progression of BW7756 murine hepatoma was investigated using intra-ocular injection with the oxyanions labeled with 75Se radioisotope. Comparison is made with the normal distribution of selenium studied by the RIXRF method. The trace elemental profiles, TEP, for the two oxidation states are compared in healthy and disease states. It has been found that the presence of tumor significantly changes the level of tracer in various uninvolved organs. These changes are prominent in the early growth phase of the tumor. The two oxidation states show differences in the TEP for kidney, spleen, stomach and testes.

Time-dependent distribution of selenate and selenite selenium in male C57L/J mice.

The distribution and retention of selenate and selenite in C57L/J mice was investigated using 75Se radioisotope. The comparison is made with the normal distribution of the element determined by using radioisotope-induced x-ray fluorescence, RIXRF methods. The distribution of the two oxidation states measured as activity of 75Se was almost identical but differed from the normal trace elemental profile, TEP. The excretion rates of the two selenium species in the initial phase are different with more selenate being excreted than selenite in the first 2 days. It was found that the wholebody excretion rates followed a pure first-order pattern this was not true for the individual organs of the animals.

Effects of heavy metals on alpha-fetoprotein in maternal sera and amniotic fluid of pregnant mice.

This report describes the effects of low levels of copper, nickel and lead salts on the concentrations of alpha-fetoprotein (AFP) in the sera and amniotic fluid of pregnant Nylar mice. During the early and mid-gestation (9-17 days), pregnant mice were injected intraperitoneally twice with heavy-metal salt solutions and were autopsied two days following the second injection. Maternal sera and amniotic fluid (AF) were collected and AFP levels were quantified by radial immunodiffusion. Metal levels determined by X-ray fluorescence spectroscopy in individual samples confirmed the presence of trace metals in the fetus. Low doses of nickel and copper were associated with elevated AFP levels in amniotic fluid in 15-17 day pregnant animals, while maternal serum AFP levels mostly remained unchanged. Decreased concentrations of maternal serum AFP occurred with increased doses of copper and lead in contrast to elevated concentrations of AFP in amniotic fluid. Furthermore, there was an increase in fetal wastage when higher doses of copper and lead were administered. A reduction of secondary litter size (F1 generation) with low dosage levels of lead was also observed. These results imply that the fetal-maternal transfer of AFP may either be impaired or reflect increased leakage or decreased placental permeability in the presence of sublethal doses of copper and lead. These findings suggest that the parallel measurements of AFP concentrations in sera and amniotic fluid might be employed for assessment of embryo- and fetotoxicity when heavy metal intake is suspected during pregnancy.

Rubidium and zinc fluctuations in selected tissues during the development of the BW7756 murine hepatoma.

In separate studies, radioisotopes 65Zn and 86Rb were used to monitor trace element fluctuations from normal in C57L/J mice throughout the progression of a murine hepatoma. Amounts too small to upset normal levels were injected directly into the blood stream. After an equilibration period, the whole mouse and various resected organs and tissues were counted. Compared to normal levels, rubidium in diseased mice was lower in kidney and blood, and elevated in skin and muscle. Diseased mice showed depressed levels of zinc in skin and muscle. Large fluctuations during different stages of tumor growth were observed for various other tissues and organs of diseased mice.

Time dependent zinc distribution in the development of the BW7756 murine hepatoma.

The Zn levels in selected tissue types were measured in a study of the BW7756 murine hepatoma utilizing 65Zn as a tracer. The total body burden and individual tissue activities (including tumor) were recorded at predetermined stages of tumor growth and directly compared to those obtained from normal (healthy) animals. 65Zn fluctuations observed with disease progression were correlated to the growth curve of the carcinoma. Normalization of individual tissue activities to the total body activity, the control of geometry and lack of significant attenuation of the accompanying gamma ray are unique advantages in the use of this isotope.

Trace element profiles in murine Lewis lung carcinoma by radioisotope-induced X-ray fluorescence.

Trace element profiles of various body tissues and tumor were established during growth of the Lewis lung tumor (LLT) with the use of radioisotope-induced X-ray fluorescence (RIXRF) analysis. The LLT, a highly malignant experimental murine tumor, resembles its human counterpart, has a well-defined life cycle, and kills its host in 30 days. When compared with normal controls, Zn, Br, and Rb levels in lung, liver, and skeletal muscle and Zn and Sr levels in bone from tumor-bearing mice exhibited large fluctuations at critical points in the tumor life cycle. In addition, the 24-day primary tumor trace element profile resembled that of its tissue of origin, normal lung, and was quite different from other normal tissues studied. These findings indicate that trace element profiles may help in the diagnosis, staging, and monitoring of disease. RIXRF is an excellent technique for this purpose because it is sensitive and relatively nondestructive of samples and has multielement capabilities.