Biokinetics and dose estimation of 65Zn in the salivary gland and male reproductive organs.

ICRP is revising its recommendations for radiological protection and has added salivary and secretory glands as new target organs. However, little information is available on the distributions of radionuclides in the salivary gland, secretory glands and male reproductive organs. This study deals with the distribution of 65Zn in the salivary gland and male reproductive organs as a function of time after a single intravenous and oral administration. For the study, 64 Wistar strain male rats, eight weeks of age were used. The rats were periodically sacrificed, the liver, kidney, spleen, pancreas, thymus, salivary gland, testis, epididymitis and prostate gland sampled and the radioactivity of these organs measured with an NaI scintillation counter. The relative concentration of 65Zn was highest in the prostate gland. We estimated the radiation dose in humans using rat data for the salivary and secretory glands as well as reproductive organs after intake of 65Zn.

Development of zinc deficiency in 65Zn labeled, fully grown rats as a model for adult individuals.

The development of zinc deficiency in adults was studied in a metabolism experiment involving 31 adult, female rats labeled homogenously with 65Zn. The animals were fed restricted amounts (8 g/day) of a semisynthetic diet containing either 58 microgram Zn/g (control, n = 7) or 2 microgram Zn/g (Zn deficiency, n = 24). Control animals were sacrificed at day 0 (n = 3) and day 29 (n = 4). Zinc deficient animals were sacrificed at day 1, 2, 4, 7, 11, 16, 22, and 29 (3 animals per group). The development of zinc deficiency comprised 4 phases: (I) Fecal Zn excretion needed several days to adjust to the low level of Zn intake. The high initial Zn loss via feces was counterbalanced mainly by Zn mobilization from the skeleton. (II) During the 2nd week of deficiency Zn mobilization from tissue storage changed transiently to soft tissues (mainly muscle and fat tissue). (III) After the 2nd week the skeleton resumed to mobilize Zn. (IV) At the end of the study the skeleton Zn storage was exhausted and alkaline phosphatase activity indicated severe Zn deficiency. Urinary Zn excretion was too small to contribute quantitatively to changes in Zn metabolism during any phase of Zn deficiency. In conclusion, adults may compensate a deficient Zn supply by mobilizing tissue Zn for several weeks: The skeleton revealed to be the major short-term as well as long-term source of whole body tissue Zn that can be mobilized.

Pharmacokinetics of intravascularly administered (65)Zinc in channel catfish (Ictalurus punctatus).

Comparison was made of the pharmacokinetics of the radioisotope (65)Zinc ((65)Zn) in blood, plasma, and whole body of adult channel catfish (Ictalurus punctatus) following intravascular (iv) administration. A two-compartment model described the pharmacokinetics of (65)Zn in plasma and blood during the first 40 days following iv administration, but was unable to describe the long-term disposition of (65)Zn. Whole-body counting revealed that approximately half of the (65)Zn dose was sequestered in a slowly exchangeable pool with a half-life of 1.5 years. Greater than 99% of the circulating (65)Zn was bound to plasma proteins, whereas there was less than 1% binding to red blood cells. Synthesis of the results for channel catfish and existing data in other species indicates three phases in the pharmacokinetics of zinc. The first phase consists of initial distribution outside the vascular system to kidney, liver, and other organs (alpha phase in blood and plasma; t(1/2) of 4 to 5 h). The second phase involves distribution from organs to a slowly exchangeable zinc pool, likely consisting of bone (beta phase in blood and plasma; alpha phase in whole body; t(1/2) of 4 to 20 days). The third phase appears to involve a slow turnover of sequestered zinc (t(1/2) greater than 1 year). Blood sampling or short-term whole-body measurements will underestimate the persistence of zinc in fish, thus prolonged sampling and measurement of whole-body concentrations are necessary to characterize the pharmacokinetics of zinc.

Zinc absorption, distribution, excretion, and retention by healthy preterm infants.

Zinc (Zn) is an essential nutrient for growth, but little is known about Zn absorption, distribution, excretion, and retention in preterm infants. Nine infants with gestational age 32+/-1 wk (mean+/-SE), birth weight 1.44+/-0.08 kg, postnatal age 14+/-3 d, on Zn intake of 23+/-3 micromol/kg per d via enteral feeding of preterm formula were studied. A stable Zn isotope (70Zn) was administered orally or i.v., and plasma, red blood cells, urine, and feces were sampled for up to 30 d. Samples were analyzed for Zn by inductively coupled plasma atomic emission spectrometry and for isotope enrichment by inductively coupled plasma mass spectrometry. Data were analyzed by compartmental analysis using the Simulation Analysis and Modeling program, and absorption, distribution, excretion, and retention were calculated. Absorption was 36+/-5% or 7+/-1 micromol/kg per d; distribution in plasma was 15+/-1 micromol Zn/L and in RBC was 41+/-4 micromol Zn/L; excretion in urine was 0.55+/-0.03 micromol Zn/kg per d and in feces was 17+/-3 micromol Zn/kg per d and retention was 5+/-1 microl/kg per d. Results show that healthy preterm infants with Zn intake of 23 micromol/kg per d and expected growth rates (> 15 g/kg per d) absorb and retain Zn at rates comparable to in utero accretion. The values for absorption, distribution, and excretion by this population of healthy preterm infants provide a normal range for future studies, although further studies are required to determine endogenous excretion rates in healthy preterm infants. We speculate that these values can be used to determine whether Zn kinetics are abnormal in sick infants or in infants with slow growth.

Biokinetics and dosimetry of chromium, cobalt, hydrogen, iron and zinc radionuclides in male reproductive tissues of the rat.

Following intravenous administration to male rats, the uptake and retention by reproductive tissues of chromium-51, cobalt-57, iron-59, zinc-65 and tritium has been studied for up to 28 days. Chromium-51, 57Co, 59Fe and 3H were not or only transiently accumulated in gonads or accessory sex glands at concentrations greater than whole body concentrations. However, 65Zn was concentrated in the dorsolateral region of the prostate gland and autoradiography showed preferential uptake by epithelial cells and lumen of glands. When combined with other information available from the literature, this data would suggest that current models adequately describe the biokinetics of chromium, cobalt, iron and tritium in the prostate and testes and zinc in the testes. Uptake of zinc by the prostate would appear to be best described by an average value of 0.1% and a conservative value of 0.5%. Allowing for greater uptake of zinc (0.5%) by the prostate, after inhalation of 65Zn in a soluble form increases prostate dose by about 3 fold compared to current models. The pessimistic assumptions of a higher relative biological effectiveness (20) for all Auger emissions from 65Zn in cell nuclei and a heterogeneous distribution of 65Zn to sensitive cells in the prostate increases prostate dose by a further factor of 9. Even on the basis of these cautions estimates, occupational exposures to radioisotopes of these elements do not explain the excess of prostate cancer reported amongst some nuclear workers.

The intestinal true absorption of 65Zn in rats is adversely affected by diets containing a faba bean (Vicia faba L.) nonstarch polysaccharide fraction.

The effects on the absorption of 65Zn by two varieties of raw faba bean (Vicia faba L., minor) or seed components that may interfere with mineral metabolism in the gut, have been studied in growing rats. In bean diets all protein was supplied by the meals, and the fractions were tested by incorporating them in control diet at the same levels as they occur in the seeds. Absorption of 65Zn was also measured in rats fed dephytinized bean meal produced by including phytase in the diet. Rats were pair-fed diets supplemented with amino acids and minerals to target requirements and containing 40 mg Zn/kg diet. True absorption of Zn was 50-70% lower in rats fed diets containing both cultivars of faba bean meals than in those fed the control diet. Although soluble nonstarch polysaccharides caused a significant reduction in the absorption of Zn, this effect disappeared after the removal of phytate by demineralization. In contrast, despite its negligible content of phytate, the insoluble nonstarch polysaccharides in the cell wall fraction of the cotyledon accounted for most of the reduction in Zn absorption in rats fed the faba bean diets. Addition of phytic acid to the control diet significantly reduced the absorption of 65Zn but only from 44 to 36%. Moreover, the increase in the absorption of Zn was similarly small, from 21% to 29%, with the addition of phytase to the faba bean diet.(ABSTRACT TRUNCATED AT 250 WORDS)

A whole body counting technique using ultralow doses of 59Fe and 65Zn in absorption and retention studies in humans.

A whole body counting technique is described which allows monitoring of gamma ray emission rates from body levels of 59Fe and 65Zn in the same range as emission rates of gamma rays from naturally occurring 40K in the total body. Consequently absorption/retention studies were performed with doses of 0.1 microCi. Experimental results from studies using corn intrinsically labeled with 65Zn and wheat intrinsically labeled with 59Fe are presented and illustrate how absorption of 59Fe as low as 4% and retention of 65Zn up to 418 days were measured in humans.

Absorption of orally administered 65Zn by normal human subjects.

Despite studies by several investigators of human gastrointestinal 65Zn absorption, implications of these data for evaluation of functional zinc status are unclear because limited numbers of normal subjects have been studied. To evaluated zinc absorption in normal humans, 75 subjects (31 women, 44 men, ages 18 to 84 yr) were given 10 micro Ci carrier-free 65Zn orally after an overnight fast. Absorption calculated from total body retention measured 7, 14, and 21 days after administration of tracer was 65 +/- 11% (mean +/- 1 SD), range from 40 to 86%. Comparison of these results with those for patients with a variety of diseases indicate that patients exhibit a wider range of absorption and, in four of six studies patients exhibit decreased mean zinc absorption. These results of gastrointestinal zinc absorption in a large number of normal humans offer a basis for a clearer comparison with data from patients who exhibit abnormalities of zinc absorption.

Zinc metabolism in humans after oral and intravenous administration of Zn-69m.

Seventeen patients were studied after separate oral and intravenous administration of 50 muCi Zn-69m to determine if Zn-69m is suitable for studying zinc metabolism in humans and to determine if the route of administration affects kinetics. Patients stayed on a metabolic ward for each study. Activity was measured in the total body, urine, feces, blood, plasma, red blood cells, and by detectors over liver and thigh. Five day urine to fecal ratios were 0.44 (intravenous), 0.018 (oral). Most activity went rapidly to liver, then followed two component exponential loss patterns in both cases. Thigh area doubling time was 5.7 days whether the zinc was given orally or intravenously. Plasma activity decreased to less than 2% of that injected by 24 hr after intravenous administration and decreased from a maximum of 1.2% of that ingested, 3 hr after oral administration to 0.7% by 24 hr. Red blood cell activity increased through the 5-day study period to maximum values of 6.4% of that injected after intravenous administration and 2.4% of that ingested after oral administration. Similar metabolic patterns were observed regardless of whether Zn-69m was administered intravenously or orally, suggesting that these patterns were not affected by the mode of administration for the cases studied.