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PubMed1989

Inactivation of transferrin iron binding capacity by the neutrophil myeloperoxidase system.

Human serum apotransferrin was exposed to the isolated myeloperoxidase-H2O2-halide system or to phorbol ester-activated human neutrophils. Such treatment resulted in a marked loss in transferrin iron binding capacity as well as concomitant iodination of transferrin. Each component of the cell-free system (myeloperoxidase, H2O2, iodide) or neutrophil system (neutrophils, phorbol ester, iodide) was required in order to observe these changes. In the cell-free system, the H2O2 requirement was fulfilled by either reagent H2O2 or the peroxide-generating system glucose oxidase plus glucose. Both loss of iron binding capacity and transferrin iodination by either the myeloperoxidase system or activated neutrophils were blocked by azide or catalase. The isolated peroxidase system had an acidic pH optimum, whereas the intact cell system was more efficient at neutral pH. The kinetics of changes in iron binding capacity and iodination closely paralleled one another, exhibiting t1/2 values of less than 1 min for the myeloperoxidase-H2O2 system, 3-4 min for the myeloperoxidase-glucose oxidase system, and 8 min for the neutrophil system. That the occupied binding site is protected from the myeloperoxidase system was suggested by 1) a failure to mobilize iron from iron-loaded transferrin, 2) an inverse correlation between initial iron saturation and myeloperoxidase-mediated loss of iron binding capacity, and 3) decreased myeloperoxidase-mediated iodination of iron-loaded versus apotransferrin. Since as little as 1 atom of iodide bound per molecule of transferrin was associated with substantial losses in iron binding capacity, there appears to be a high specificity of myeloperoxidase-catalyzed iodination for residues at or near the iron binding sites. Amino acid analysis of iodinated transferrin (approximately 2 atoms/molecule) demonstrated that iodotyrosine was the predominant iodinated species. These observations document the ability of neutrophils to inactivate transferrin iron binding capacity via the secretion of myeloperoxidase, formation of H2O2, and subsequent myeloperoxidase-catalyzed iodination. This sequence of events may help to explain the changes in iron metabolism associated with the in vivo inflammatory response.

Amino Acids↗

PubMed1989

The diagnosis of CSF fistulae on the basis of detection of beta 2-transferrin by polyacrylamide gel electrophoresis and immunoblotting.

A sensitive method is described for the detection of beta 2-transferrin, a transferrin-variant found only in cerebrospinal fluid (CSF). The determination of beta 2-transferrin, whose presence is characteristic of CSF-admixtures in secretions, is performed in three steps. The proteins of the secretion are separated by polyacrylamide gel electrophoresis and then transferred electrophoretically onto a nitrocellulose sheet. Finally, the transferrins on the nitrocellulose sheet are specifically detected by an antibody reaction. The bands are visualized either by using antibodies conjugated with peroxidase or by protein A gold. With the exception of certain cases (Ritchie, R. F. & Smith, R. (1976) Clin. Chem. 22, 497-499; Görg, A. et al. (1983) Human Genetics 64, 222-226) beta 2-transferrin is found only in cerebrospinal fluid, and not in other body fluids. Therefore the detection of beta 2-transferrin can be used for the diagnosis of rhino- and otoliquorrhea. The advantage of this method is that beta 2-transferrin can be unequivocally identified by the use of a relatively small amount of technical equipment. CSF can therefore be clearly identified in secretions. An additional advantage of the method is its high sensitivity.

Blotting, Western↗

PubMed1988

Endocytosis of the transferrin receptor is altered during differentiation of murine erythroleukemic cells.

During terminal differentiation of murine erythroleukemic (MEL) cells, the number of surface transferrin binding sites per cell decreases dramatically, while steady-state ligand uptake and immunoblotting studies demonstrate that the total number of transferrin receptors per cell remains constant. Since the amount of protein per cell decreases 4-fold during this 4-day period, the amount of transferrin receptor protein, relative to total soluble cell protein, increases 4-fold during this time, suggesting continued synthesis of the receptor. Supporting this, we show that the amount of transferrin receptor transcript in equal amounts of total cell RNA also increases as differentiation proceeds. Uninduced cells maintain 52% of the total transferrin binding sites on the cell surface, whereas only 22% of the receptors are on the surface in 4-day induced cells. All ligand endocytosed by either uninduced or induced cells at 37 degrees C is rapidly and completely exocytosed from the cells, suggesting that all of the cellular receptors are cycling. These studies suggest that, during MEL cell differentiation, an increasing fraction of transferrin receptors are localized to the cell interior, but are nevertheless cycling to the cell surface. This observed redistribution is due to altered kinetic parameters of the receptor. Receptor-bound 125I-labeled transferrin ligand has been followed through a single endocytic cycle. Ligand internalization occurs much more rapidly in induced cells (t1/2 = 2.9 min) than in uninduced cells (t1/2 = 6.9 min). The rates for ligand movement back out to the cell surface and its subsequent release into the medium in both uninduced and induced cells are quite similar.

Algorithms↗

PubMed1987

[New methods of diagnosing cerebrospinal fluid fistulas using beta 2-transferrin or prealbumin--principles and methodology].

Two new methods were developed to identify pure CSF and CSF in nasal secretion. One method is based on measurement of beta 2-transferrin, a transferrin variant found only in CSF, whereas the other one is based on determination of the albumin-prealbumin ratio. The determination of beta 2-transferrin is made in two steps. Firstly, the protein variants beta 1- and beta 2-transferrin are isolated selectively from the complex protein mixture by an affinity procedure. The transferrin variants are then separated by a highly resolving polyacrylamide gelelectrophoresis and identified by staining. Advantages of the method are that blood or nasal secretion does not disturb the test and that beta 2-transferrin can be identified with high accuracy. Therefore, CSF can be differentiated unambiguously from other secretions. The determination of the ratios of concentration of the proteins albumin and prealbumin by immunoelectrophoresis is a further possibility to identify pure or almost pure CSF. This sensitive method, which is fast and easy to perform, is very helpful in corroborating the diagnosis of a CSF fistula. On the basis of this method one cannot get a false positive result, but a false negative one by high contamination of CSF with blood or nasal secretion. Therefore, the method of beta 2-transferrin determination must be carried out if there is any doubt.

Cerebrospinal Fluid Otorrhea↗

PubMed1987

Removal of transferrin from fetal bovine serum.

An antiserum against purified fetal bovine serum (FBS) transferrin was produced in rabbits. The isolation of anti-bovine transferrin IgG fraction was achieved by ammonium sulfate precipitation of rabbit hyperimmune plasma followed by ion exchange chromatography on diethylaminoethanol (DEAE) cellulose, at both an acidic and basic pH. The various antibody fractions were analyzed by fast protein liquid chromatography (FPLC) on a high-resolution mono-Q column. The specificity and efficiency of the antibody fractions obtained were tested by titration of a constant amount of fetal bovine serum with increasing amounts of antibody. The completeness of removal of the fetal bovine serum transferrin resulting from the formation of the highly stable antibody antigen complex was monitored by immunologic and radioisotope methods. The removal of FBS transferrin by this antibody precipitation technique did not interfere with the ability of added iron 59-tagged human transferrin to deliver iron to rat reticulocytes, as shown in an in vivo incubation model. The method proved to be effective for the fast and complete removal of bovine transferrin from fetal bovine serum in vitro and will be a prerequisite for more detailed studies of the interaction of transferrin of different species with tissue receptors on cell lines in culture without resorting to completely defined culture media.

Animals↗

PubMed1986

Albumin and transferrin synthesis in whole rat embryo cultures.

The uptake of [3H]leucine by the rat yolk sac and embryo and the subsequent synthesis of albumin and transferrin have been studied in whole embryo culture. Rat embryos of 12 days gestation were used in all experiments. Isotopically labelled transferrin was detectable in yolk-sac and embryo tissue extracts. In contrast, [3H]albumin could not be found in either tissue extract. Levels of radioactive transferrin in the yolk sac of cultured whole conceptuses decreased during 12 h in cold media. Embryonic transferrin showed an opposite trend in that it increased over 12 h by nearly 30-fold. In view of these results experiments were conducted in embryos and yolk sacs cultured in separate bottles. Radioimmunoprecipitation for transferrin revealed that there was synthesized protein in the yolk sac which then decreased by approximately 30% after 2 h in normal cultured medium. There was no evidence of transferrin synthesis in embryo extracts over a 12 h period. These results present evidence that the visceral yolk sac is the primary site of transferrin synthesis in the rat and that the protein is thereafter transported, intact, to the embryo.

Albumins↗

PubMed1986

Seminal transferrin, an index of Sertoli cell function: is it of clinical value?

To determine the clinical value of seminal transferrin measurements, transferrin concentrations in seminal plasma were determined by single radial immunodiffusion. Men with various disorders of spermatogenesis had significantly lower mean values than those with normal semen (170 micrograms/ejaculate, s.e.m. = 18.4), oligospermia (40.5 micrograms, s.e.m. = 7.2) or azoospermia due to primary seminiferous tubule failure (65.9 micrograms, s.e.m. = 29.1). In these subjects with patent genital tracts, seminal transferrin was directly correlated with sperm concentration and indirectly correlated with serum FSH levels. Seminal transferrin increased following gonadotrophin treatment of men with gonadotrophin deficiency from 19.6 micrograms (s.e.m. = 5.5) to 108.6 micrograms (s.e.m. = 31.7). Patients with genital tract obstructions also had low levels; vasal agenesis (21.8 micrograms, s.e.m. = 5.6), vasectomy (48.5 micrograms, s.e.m. = 21.0), epididymal obstruction (46.6 micrograms, s.e.m. = 7.1). These results confirm that most seminal transferrin comes from the testes and reflects Sertoli cell function. However, there is a very wide range of transferrin levels in normal semen and a number of normospermic samples have low values similar to those seen with abnormal Sertoli cell function or obstruction. Thus, measurement of seminal transferrin is of limited diagnostic value.

Genital Diseases, Male↗

PubMed1985

[Rapid analysis of transferrin-iron complexes by isoelectric focusing and radioactive densitometry on gel].

The analysis of the molecular forms of transferrin-iron complexes with 59Fe, was carried out using an isoelectric focusing method on commercially available polyacrylamide plates (PAG plates pH = 4-6,5, LKB). Depending upon the saturation degree of proteins with iron, apotransferrin (pI = 6,1), transferrin-Fe3+ (pI = 5,8), transferrin-2 Fe3+ (a) (pI = 5,5) and transferrin-2 Fe3+ (b) (pI = 5,3) were put forward. When the protein was saturated with iron, a double band was observed which was assigned to the microheterogeneity of the protein and depends upon the sialic content. The quantitative analysis was carried out by studying 59Fe radioactivity distribution directly on the plate. As a control, a specific staining of proteins was achieved. The interpretation of the results is difficult if such a method is used, as some bands are not attributed. Through an unspecific staining, the UV-visible densitometry is not satisfactory enough. The proposed method allows a fast analysis of transferrin-metal complexes labeled with radioactive metals. Such a method would be adaptable to the study of other complexes as transferrin-67Ga, transferrin 111In in order to determine the binding site of metal on the protein and its metal content.

Densitometry↗

PubMed1983

Peptide mapping of the human transferrin receptor in normal and transformed cells.

Human transferrin receptor protein from various human cell lines in tissue culture (phytohemagglutinin-activated lymphocytes, normal embryonic fibroblasts (WI-38), a choriocarcinoma (Be Wo), an epidermoid carcinoma (KB), and a metastatic breast carcinoma (MCF-7)) was metabolically labeled with [35S]methionine and purified by two methods. The first method involves affinity chromatography of the transferrin receptor with a transferrin-linked Sepharose 4B resin. The second method involves direct immunoprecipitation of the receptor protein with a goat polyclonal antibody raised against placental transferrin receptor. Additionally, transferrin receptor from normal gestational placenta was similarly radiolabeled with [35S]methionine and subsequently purified with transferrin-bound resin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the reduced receptor isolated by both purification techniques revealed an Mr = 94,000 protein to be present in all cells assayed for this study. Partial proteolytic digestion with Staphylococcus aureus protease followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed identical mapping patterns of the Mr = 94,000 protein isolated from each cell line, irrespective of the isolation technique employed to purify the receptor. These findings indicate an identical peptide structure of the human transferrin receptor in cells with a differentiated function for iron metabolism, in normal cells undergoing mitosis, and in neoplastic cells in long term culture, within the limits of detectability of the proteolytic digestion maps.

Cell Division↗

PubMed1983

The significance of transferrin for intestinal iron absorption.

A mechanism is proposed by which apotransferrin is secreted from mucosal cells, loaded with iron in the intestinal lumen, and then the intact complex is taken into the cell. Within the cell, iron is released and transferred to the blood stream, whereas iron-free transferrin returns to the brush border to be recycled. We have investigated this hypothesis by measuring intestinal absorption of radioiron and 125I-labeled plasma transferrin using tied-off gut segments in normal and iron-deficient rats. There was no absorption of diferric transferrin from the ileum, but high absorption from the duodenum and jejunum segments. Jejunal absorption occurred as a function of the dose offered and showed saturation kinetics. In normal animals, 4 micrograms of the 50 micrograms of transferrin iron was absorbed over 1 hr. In iron-deficient animals, mean values as high as 13 micrograms were observed. Radioiron content of the jejunal mucosa bore a linear relationship to the dose administered and was inversely proportional to the amount of iron entering the plasma. Recycling of transferrin was indicated by the presence of labeled apotransferrin in the lumen, first observed between 15 and 60 min after the injection of diferric transferrin. A high resistance of diferric and apotransferrin to proteolytic degradation within the gut lumen was demonstrated. Comparative studies with lactoferrin and ferritin disclosed poor availability of their iron for absorption. The small amount that was absorbed did not relate to the iron status of the recipient animal. These studies support the role of mucosal transferrin as a shuttle protein for iron absorption.

Anemia, Hypochromic↗

PubMedDate not supplied

CFS transferrin in various neurological diseases.

The introduction of isoelectrofocusing on polyacrylamide gel followed by direct immunofixation, in the analysis of CSF proteins, emphasized the interest in transferrin examination, mainly in order to find eventual abnormalities in patients with neurological diseases. Stibler (1979), using these techniques, demonstrated the presence in CSF of two subtypes of transferrin C, called C1 and C2, transmitted by autosomal codominant inheritance, according to the C1, C2 and C2-1 phenotypes. The rather frequently occurring variant of transferrin in CSF is the C2-1 subtype: a double banded pattern, which is focused at pH 5.9, consisting of two very closely spaced bands with a pI difference of less than 0.1. This transferrin pattern is peculiar to CSF and is absent in the serum of the same subjects. This subtype of transferrin has been observed in various neurological disorders, as well as in healthy populations, by several investigators. They also found a much higher incidence of double tau-transferrin in inherited degenerative neurological diseases, such as Friedreich's ataxia and hereditary spastic paraplegia, than in neurological ailments without a hereditary component. The aim of our study is to verify the incidence of the C2-1 variant of transferrin in a control group and in a mixed group of neurological patients, with particular attention to hereditary degenerative pathologies.

Humans↗

PubMed1995

Immunohistochemical detection of alpha 1-antitrypsin, alpha 1-antichymotrypsin, transferrin and ferritin in ameloblastoma.

An immunohistochemical study was performed to investigate the presence of alpha-1-antitrypsin (alpha 1-AT), alpha-1-antichymotrypsin (alpha 1-ACT), transferrin and ferritin in 32 ameloblastomas and to evaluate the co-expression of these antibodies. Histologically, we recognized the following 6 patterns in the series of 32 ameloblastomas and at least 2 patterns in variable proportions were present in each of our cases: follicular pattern (21 cases, 66%), plexiform pattern (17 cases, 53%), cystic pattern (21 cases, 66%), acanthomatous pattern (10 cases, 31%), granular cell type (2 cases, 6%), and hyalinized stromal pattern (20 cases, 63%). Neoplastic epithelia of cystic pattern were divided into superficial cell, basal cell and whole layer to compare the immunohistochemical localization. The results made on the various patterns of ameloblastomas were as follows: (1) alpha 1-AT positivity in plexiform, cystic and hyalinized stromal patterns was significantly higher than that of alpha 1-ACT (P < 0.05). (2) The incidence of transferrin in follicular and plexiform patterns was markedly higher than that of ferritin in the same patterns (P < 0.025 and P < 0.01). Transferrin strongly stained metaplastic squamous cells of acanthomatous pattern and basal cells of cystic epithelium. (3) Granular cells reacted with transferrin and ferritin. (4) In follicular and acanthomatous patterns, coexpression of alpha 1-AT and alpha 1-ACT, alpha 1-AT and transferrin, or alpha 1-ACT and transferrin was higher than that of another combination. On the other hand, co-expression of alpha 1-AT and transferrin in plexiform and cystic patterns was higher than that of other antibodies. These results of co-expression of 4 antibodies used in the present study, suggest that the histogenesis of follicular and acanthomatous patterns is different from that of plexiform and cystic patterns.

Adolescent↗

PubMed1995

Effect of hydroxyurea on cellular iron metabolism in human leukemic CCRF-CEM cells: changes in iron uptake and the regulation of transferrin receptor and ferritin gene expression following inhibition of DNA synthesis.

Hydroxyurea inhibits cellular proliferation through action on ribonucleotide reductase, an iron-dependent enzyme responsible for the synthesis of deoxyribonucleotides. Whereas previous investigations have examined the interaction of hydroxyurea with this enzyme, the action of hydroxyurea on other aspects of iron metabolism has not been studied in detail. In our study, incubation of CCRF-CEM cells with hydroxyurea resulted in an inhibition of ribonucleotide reductase activity/DNA synthesis within 4 h and produced a parallel decrease in the uptake of iron by cells. In contrast, iron uptake by hydroxyurea-resistant CCRF-CEM cells was not inhibited by hydroxyurea. After 6 h, hydroxyurea produced an increase in the activity of the iron-regulatory protein, a cytoplasmic mRNA-binding protein responsible for regulating the translation of transferrin receptor and ferritin mRNAs. After 24 h, hydroxyurea-treated cells displayed a 1.5-fold increase in transferrin receptor mRNA and protein and a significant decrease in ferritin levels. The hydroxyurea-induced increase in transferrin receptor was abrogated by transferrin-iron. In contrast to hydroxyurea, inhibition of DNA synthesis by 1-beta-D-arabinofuranosylcytosine produced a decrease in transferrin receptor expression. Our studies suggest that iron uptake by CCRF-CEM cells is closely linked to ribonucleotide reductase activity rather than to transferrin receptor number. Inhibition of ribonucleotide reductase/DNA synthesis by hydroxyurea results in a decrease in iron uptake by cells and an increase in the activity of the iron-regulatory protein, which, in turn, is responsible for the hydroxyurea-induced increase in transferrin receptor and decrease in ferritin synthesis.

Antineoplastic Agents↗

PubMed1995

Translocation of different forms of transferrin from blood to bile in the rat.

Five different forms of transferrin (rat apo [iron-free], rat diferric, diferric rat asialo, human diferric, and diferric human asialotransferrin type 3) were used to monitor the passage of this protein and its metal to the bile. Cumulative biliary excretion of the dose over 3 hours was determined. In addition, an excretion profile was constructed from the concentration of tracer in bile samples collected over 10-minute intervals. The profile obtained with apotransferrin was very similar to that found in an earlier study with albumin, the implication being that the apo form is transferred passively (e.g., by diffusion). Behavior of rat diferric transferrin, however, was consistent with the assumption that this form is transferred both passively and actively (i.e., in vesicles). The three other transferrins were investigated with the intent of broadening the spectrum of ligand affinities for the plasmalemma of hepatocyte. The higher this attraction was, the larger fraction of the dose appeared in bile. When transferrin was targeted to lysosomes, the bile contained several intermediate proteolytic fragments. Double-labeled (125I, 59Fe) transferrin was used to measure recovery of iron (Fe) relative to the protein (P) in bile. With rat diferric transferrin, the Fe/P ratio was 0.72. Lower values were recorded with transferrins (human or asialo) that had higher affinities for the plasmalemma and therefore were expected to be transported to a larger extent in vesicles. Of the biliary 59Fe, 85% to 92% was protein bound. The proportion of the protein-bound fraction was essentially independent of the magnitude of Fe/P ratios.

Animals↗

PubMed1993

Exogenous antigens internalized through transferrin receptors activate CD4+ T cells.

The role of endosomes in exogenous Ag processing was investigated by targeting Ag into the endosomal transport pathway via transferrin receptors. The Ag, pigeon cytochrome c and chicken OVA, were coupled to human ferric transferrin by a heteroligation technique. The conjugates were significantly more efficient than native Ag in stimulating Ag-specific CD4+ T cells, when the APC expressed transferrin receptors. The addition of ferric transferrin eliminated the enhanced response. Paraformaldehyde-fixed APC did not present the conjugates, indicating that the conjugates still required processing to activate T cells. An augmented level of T cell activation was not observed when the APC lacked transferrin receptors or when the conjugate contained the apoenzyme form of transferrin, which does not bind the receptor. The conjugate followed an intracellular pathway similar to that for transferrin, remaining in low density vesicles. Degraded conjugate appeared rapidly in culture supernatants, within 5 min, and peaked by 20 min; under these conditions a T cell response to the conjugate was elicited that was consistent with an early processing compartment. Our results suggest that antigenic peptide fragments can be generated in the early endosomes, without delivery of these Ag to the lysosomes. Thus, various Ag may have differential processing requirements, dictated by their molecular nature, that determine the site of Ag processing.

Animals↗

PubMed1993

Beta-2 transferrin assay in clinical management of cerebral spinal fluid and perilymphatic fluid leaks.

Beta-2 transferrin is a protein found in cerebral spinal fluid (CSF) and inner ear perilymph, but not in blood, nasal or ear secretions. The purpose of this paper is to evaluate the clinical usefulness of the current assay for beta-2 transferrin for detecting CSF and perilymphatic leaks. We reviewed the hospital records of the first 88 patients having specimens submitted for beta-2 transferrin analysis at our institution. Both CSF and perilymph leaks were identified. However, confirmation of the absence or presence of beta-2 transferrin was directly used in the clinical management of only 55% of the patients. This was largely secondary to the time delay in test processing and initial lack of physician confidence with the test. However, our review of the clinical outcomes relating to the use of the beta-2 transferrin analysis suggests high sensitivity and specificity for the test. Analysis of beta-2 transferrin appears to be a valuable test for detecting CSF leakage and a promising test for confirming perilymphatic leaks. However, to achieve greater clinical usefulness a rapid clinical assay needs to be developed and further information gained regarding the sensitivity and specificity of the beta-2 transferrin assay for detecting CSF and perilymphatic fluid leakage.

Adult↗

PubMed1997

Phosphatidylinositol 3-kinase inhibitor wortmannin blocks mitogenic activation of the transferrin receptor gene promoter in late G1.

Expression of the transferrin receptor is necessary for cells to progress through S-phase. The transferrin receptor gene promoter is activated as a delayed event following growth factor stimulation of quiescent fibroblasts. Serum stimulation in the presence of vanadate leads to superactivation of the transferrin receptor promoter, suggesting a role for tyrosine phosphorylation. Wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, a tyrosine kinase-regulated enzyme, blocks mitogen-dependent activation of the transferrin receptor promoter. Furthermore, wortmannin was able to block activation of this promoter when added several hours after serum stimulation of quiescent cells. This suggests that phosphatidylinositol 3-kinase may be required in mid to late G1 and that it is directly involved in a pathway leading to activation of the transferrin receptor promoter. This is further supported by the finding that the transferrin receptor promoter is much less responsive to mitogenic stimulation in cells that have been stably transfected with a dominant negative form of the phosphatidylinositol 3-kinase regulatory subunit. Activation of S6 kinase, an event known to be downstream of phosphatidylinositol 3-kinase activation, appears not to be involved in activation of the transferrin receptor promoter since no effect was observed by treatment of cells with rapamycin.

3T3 Cells↗

PubMed1998

Transferrin-dependent uptake and dosimetry of Auger-emitting diagnostic radionuclides in human spermatozoa.

UNLABELLED: Localization of Auger-emitting radionuclides within spermatozoa could lead to the induction of transmissible genetic damage. We have quantified in vitro uptake of the widely used diagnostic Auger-emitters, (111)In and 99mTc, by ejaculated human spermatozoa and investigated the role of transferrin in their cellular localization. The resultant dose to sperm heads, including cellular dosimetry for Auger emissions, has been calculated for each radionuclide and compared with that achieved using conventional macrodosimetry. METHODS: Freshly isolated human spermatozoa were incubated in a physiological salt solution containing (111)In-chloride, 99mTc-pertechnetate or the transferrin-binding isotope 59Fe-citrate as a positive control. Cellular uptake mechanisms were investigated with transferrin competition and temperature dependence studies. The percentage uptake of each radionuclide was determined, and the dose to individual sperm heads was calculated using both conventional macrodosimetric methods and by consideration of radionuclide localization and energy deposition at the cellular level, including Auger electron emissions from (111)In and 99mTc. RESULTS: On in vitro incubation, human spermatozoa were found to accumulate (111)In and 59Fe but not 99mTc. Cell uptake of (111)In and 59Fe was transferrin-mediated; however, an alternative transferrin-independent uptake pathway was also present for (111)In. The dose to sperm heads from (111)In, calculated using measured uptake and cellular dosimetry, was found to be larger than that calculated using conventional dosimetry by a factor of more than 100. In contrast, conventional dosimetry was adequate for 99mTc and 59Fe. CONCLUSION: Isolated human spermatozoa appear to accumulate transferrin-binding isotopes, such as the Auger-emitter (111)In. If this uptake mechanism operates in the male reproductive tract, the resultant high dose to the sperm head could indicate that contraception may be advisable after large diagnostic doses of (111)In and, possibly, other transferrin-binding radionuclides. Such precautions could prevent transmission of any genetic damage from irradiated spermatozoa.

Humans↗