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PubMed1998

Expression of a plastidic ATP/ADP transporter gene in Escherichia coli leads to a functional adenine nucleotide transport system in the bacterial cytoplasmic membrane.

Recently, a second type of eucaryotic adenine nucleotide transporter located in the inner envelope membrane of higher plants has been identified at the molecular level (Neuhaus, H. E., Thom, E., Möhlmann, T., Steup, M., and Kampfenkel, K. (1997) Plant J. 11, 73-82). Here we have analyzed the biochemical properties of this ATP/ADP transporter from Arabidopsis thaliana (AATP1, At). This analysis was carried out by expressing a cDNA encoding this carrier as a histidine-tagged chimeric protein heterologously in Escherichia coli. Isopropyl-1-thio-beta-D-galactopyranoside (IPTG)-induced E. coli cells were able to import radioactively labeled [alpha-32P]ATP. Uninduced E. coli cells did not import [alpha-32P]ATP. Further control experiments revealed that IPTG induction did not promote import of other phosphorylated or unphosphorylated metabolites into the bacterial cell indicating the specificity of [alpha-32P]ATP transport. [alpha-32P]ATP uptake into induced E. coli cells was linear with time for several minutes allowing for determination of kinetic constants. The apparent Km for ATP was 17 microM which is close to values reported on the authentic protein in isolated plastids. ADP was a strong competitive inhibitor of -alpha-32P-ATP uptake (Ki ADP 3.6 microM). Other metabolites like AMP, ADP glucose, UTP, UDP, NAD, and NADP did not influence [alpha-32P]ATP uptake. IPTG-induced E. coli cells preloaded with [alpha-32P]ATP exported radioactively labeled adenylates after exogenous addition of unlabeled ATP or ADP indicating a counter exchange mechanism of transport. The biochemical properties of the heterologously expressed AATP1 gene product demonstrated that the protein is functionally integrated in the cytoplasmic membrane of E. coli. This is the first report of the functional expression of a plant membrane protein in E. coli leading to new transport properties across the cytoplasmic membrane. The functional integration of a plant membrane protein in the cytoplasmic membrane of E. coli offers new possibilities for future studies of the structural and mechanistic properties of this transporter. Since IPTG induction allowed synthesis of a 67-kDa protein in E. coli, which was subsequently specifically enriched by metal-chelate chromatography, this procaryotic heterologous expression system might provide a suitable system for overproduction of membrane proteins of eucaryotic origin in the near future.

Adenine Nucleotides↗

PubMed1986

The effect of chelating agents on the distribution of monoclonal antibodies in mice.

The potential for altering the biodistribution of radiolabel from gallium- and indium-labeled mouse monoclonal antibodies was investigated in mice using metal chelating agents. The chelating agents used were desferrioxamine (DFO), diethylenetriaminepentaacetic acid (DTPA), ethylenediamine-di (O-hydroxyphenylacetic acid) (EDHPA), and 2,2' dipyridyl (DIPY). The mouse monoclonal antibody LICR-LON-M8 was labeled with 111In after conjugation to DTPA, and with 67Ga after conjugation to DFO. All the chelating agents except DIPY altered the biodistribution of [67Ga]citrate and [111In]citrate but did not affect the 48-hr tissue uptake of label from [111In]DTPA-M8 or [67Ga]DFO-M8, confirming the in vivo stability of the antibody conjugates. Label fixed in the tissues was inaccessible to the chelating agents, indicating that they will not be suitable for reducing the high background liver radioactivity in patients undergoing scanning with indium-labeled antibodies.

2,2'-Dipyridyl↗

PubMed1998

Design of metal-binding green fluorescent protein variants.

Diglycylcysteine motifs bind reduced oxo-compounds of technetium-99m, an important isotope in nuclear imaging. We suggested a system for detecting gene expression employing the effect of oxo[99mTc]technetate (Tc(V)O3+) transchelation and coordination with redox amino acid motifs. DNA fragments encoding diglycylcysteine (GGC) binding motifs were prepared by PCR and positioned downstream from the green fluorescent protein (GFP) cDNA insert. Using a Bluescript (+) vector with the fusion protein positioned under the control of a lac promoter, we obtained several E. coli clones expressing the following GFP fusion peptides: (1) GFP-P1 bearing a 'hydrophilic' C-terminal peptide (LEGGGCEGGC) containing two residues of glutamic acid and C-terminal cysteine (2) GFP-P2 carrying a 'hydrophobic' (LGGGGCGGGCGI) peptide (3) a control GFP fusion peptide with deleted C-terminal portion. Bacterial lysates obtained from the corresponding clones were tested for oxo[99mTc] technetate transchelation from a glucoheptonate complex. We found, using a solid phase assay, that radioactivity associated with protein lysates obtained from clones expressing GFP-P2 fusions were 3-4 fold higher than lysates prepared from a clone expressing a truncated GFP fusion protein lacking the C-terminal GGC motifs. High expression of GFP fusions (5-21% of total protein) was demonstrated by electrophoresis and verified by immunoblotting. Specific association of the isotope with GFP-P2 fusion proteins was detected upon incubation of gels in the presence of [99mTc]glucoheptonate, while no binding of oxo[99mTc]technetate to GFP-P1 was revealed. We demonstrated, by using semi-quantitative autoradiography, that there is a 10-fold higher binding of oxotechnetate to GFP-P2 than to a control GFP fusion protein. The implications of the study for in vivo gene expression imaging are discussed.

Amino Acid Sequence↗

PubMed2001

Comparison of fluorescence and rinsing methods for assessing dermal exposure.

There are a number of methods of estimating dermal contamination. "Potential exposure" methods, such as patch and whole-body oversuit sampling, intercept the contaminant before it reaches the skin. "Actual exposure" measurements recover the contaminant from the skin by wiping, stripping, or rinsing, or, in the case of fluorescent tracer dye monitoring, assess it in-situ on the skin. These different methods can give rise to very different results. Comparison of methods is difficult, because they usually interfere within-subject. This presentation is a comparison of two compatible 'actual dermal contamination' measurement techniques. They are: (1) fluorescence monitoring of a tracer dye in-situ on the skin, using ultraviolet light and a video camera linked to an image processor; (2) rinsing of the skin to recover a metal tracer salt for later assay in solution. Several painting and spraying application tasks were carried out by a panel of volunteers who wore T-shirts, shorts, and open sandals. The exercises simulated domestic or nonoccupational tasks. Results showed excellent agreement, with discrepancies identified and explained. The good agreement of the two completely different, independent tracer methods for measuring skin contamination contributes to their mutual validation.

Environmental Exposure↗

PubMed1992

Accumulation of Cd(II) in the CNS depending on the route of administration: intraperitoneal, intratracheal, or intranasal.

The uptake and subsequent neuronal transport of certain heavy metals in the olfactory mucosa may be a major means by which these compounds gain access to the CNS. To contrast olfactory versus blood-borne routes of exposure, three groups (n = 4) of adult Long-Evans rats were exposed to solutions of radiolabeled CdCl2. Exposure was by one of three routes: unilateral intranasal instillation (IN), intratracheal lavage (IT), or intraperitoneal injection (ip). The dose level for the intranasal route was 30 microliters of 1 microM CdCl2 labeled with 1 microCi 109Cd. For IT and ip, the dose was 30 microliters of 1 microM CdCl2 diluted to 300 microliters in saline and labeled with 1 microCi 109Cd. Rats were euthanized 24 hr after exposure, tissue samples were taken, and radioactivity was counted. Cd levels were low in the olfactory bulbs of rats exposed either intratracheally or intraperitoneally. However, in rats intranasally exposed, Cd levels were nearly 40 x higher in olfactory bulbs ipsilateral to the exposed side than in those on the contralateral side. With all routes of exposure, Cd levels in brain samples were only slightly elevated. These results suggest that for certain airborne toxicants, especially those that are excluded from the CNS by the blood-brain barrier, the olfactory system may provide a direct route of entry into the CNS.

Administration, Intranasal↗

PubMed2006

210Pb dating of sediments in a heavily contaminated drainage channel to the La Plata estuary in Buenos Aires, Argentina.

Concentrations of (210)Pb and (137)Cs in sediment samples collected from two cores at a drainage channel to the La Plata river estuary in Buenos Aires, Argentina, were measured using ultralow-background detection systems. The (210)Pb data were used to determine the rate of sediment accumulation of the sites. These results were correlated with some heavy metal (chromium and lead) concentrations of the samples in an attempt to characterize the historical input of contaminants due to the industrial development, which has taken place in this area over the last century. The (137)Cs measurements demonstrate that cesium dating is not adequate in regions of the southern hemisphere.

Argentina↗

PubMed2005

Selective removal of 226Ra2+ from gas-field-produced waters.

The 226Ra2+ selectivity of both the self-assembled (iso)-guanosine-based systems and ionizable thiacalix[4]crown dicarboxylic acids was determined in gas-field-produced water and a metal ion-containing model solution (simulant). Seven gas-field-produced water samples have been analyzed. From a sample (K5D) with average metal ion concentrations ([metal(tot)] = 0.14 M), thiacalix[4]crown-5 dicarboxylic acid (10(-4) M) extracts 60% of the 226Ra2+ content. Extractions performed with the model solution ((M)K5D) indicate that in K5D there is significant competition in 226Ra2+ extraction due to the organic constituents of K5D, in particular with self-assembled extractants guanosine and isoguanosine. Nevertheless, all four extractants extract 226Ra2+ both from the produced water K5D and the model solution (M)K5D, even with a 100-fold excess of [metal(tot)] to [extractant]. The extracted 226Ra2+ cations could effectively be stripped from the extractants bywashing with pH 2 water. The results obtained with the extractants used, especially thiacalix[4]crown-5 dicarboxylic acid 3, clearly demonstrate the way to selectively remove Ra2+ from gas-field-produced waters.

Crown Compounds↗

PubMed2003

Release of substituents from phenolic compounds during oxidative coupling reactions.

Phenolic compounds originating from plant residue decomposition or microbial metabolism form humic-like polymers during oxidative coupling reactions mediated by various phenoloxidases or metal oxides. Xenobiotic phenols participating in these reactions undergo either polymerization or binding to soil organic matter. Another effect of oxidative coupling is dehalogenation, decarboxylation or demethoxylation of the substrates. To investigate these phenomena, several naturally occurring and xenobiotic phenols were incubated with various phenoloxidases (peroxidase, laccase, tyrosinase) or with birnessite (delta-MnO(2)), and monitored for chloride release, CO(2) evolution, and methanol or methane production. The release of chloride ions during polymerization and binding ranged between 0.2% and 41.4%. Using the test compounds labeled with 14C in three different locations (carboxyl group, aromatic ring, or aliphatic chain), it was demonstrated that 14CO(2) evolution was mainly associated with the release of carboxyl groups (17.8-54.8% of the initial radioactivity). Little mineralization of 14C-labeled aromatic rings or aliphatic carbons occurred in catechol, ferulic or p-coumaric acids (0.1-0.7%). Demethoxylation ranged from 0.5% to 13.9% for 2,6-dimethoxyphenol and syringic acid, respectively. Methylphenols showed no demethylation. In conclusion, dehalogenation, decarboxylation and demethoxylation of phenolic substrates appear to be controlled by a common mechanism, in which various substituents are released if they are attached to carbon atoms involved in coupling. Electron-withdrawing substituents, such as -COOH and -Cl, are more susceptible to release than electron-donating ones, such as -OCH(3) and -CH(3). The release of organic substituents during polymerization and binding of phenols may add to CO(2) production in soil.

Carbon Dioxide↗

PubMed1995

Synthesis, pharmacokinetics, and biodistribution of 67GA deferoxamineacetyl-cysteinylbiotin.

The exceptionally high affinity of streptavidin for biotin may be exploited for two-step in vivo approaches for delivering radiolabelled biotin derivatives to lesion-bound streptavidin-conjugated monoclonal antibodies. A radiolabeled biotin derivative was prepared, and its characterization, stability, pharmacokinetics, and biodistribution studies are presented. This derivative contains deferoxamine, a chelating moiety with high affinity for trivalent metals suitable for imaging and therapy. Deferoxamineacetyl-cysteinylbiotin (DACB) was synthesized in three steps: nucleophilic reaction of deferoxamine with N-hydroxysuccinimide iodoacetate, aminolysis of N-hydroxysuccinimide biotin by L-cysteine, followed by coupling of cysteinylbiotin with N-iodoacetyldeferoxamine. DACB was characterized by matrix-assisted laser desorption/ionization MS. Radiolabeling of DACB with 67Ga led to a labeling efficiency of > 95%. Pharmacokinetics of 67Ga DACB exhibited rapid blood clearance, with < 10% circulating at 30 min and < 1% at 6 hr. Plasma samples collected at various time intervals showed > 95% binding with streptavidin, indicating in vivo stability of 67Ga DACB. Urinalysis showed > 80% of the administered dose excreted at 6 hr. Biodistribution data at 6 hr showed < 1% radioactivity remaining per organ.

Animals↗

PubMed2001

Thermodynamic stability and kinetic inertness of MS-325, a new blood pool agent for magnetic resonance imaging.

Stability constants were measured for complexes formed between a modified DTPA ligand and the metal ions Gd(III), Eu(III), Fe(III), Ca(II), Cu(II), and Zn(II) at 25 degrees C in 0.1 M NaClO4. The gadolinium complex of this ligand is MS-325, a novel blood pool contrast agent for magnetic resonance imaging currently undergoing clinical trials. Stability constants were determined by 4 different methods: direct pH titration, pH titration with competition by EDTA, competition with DTPA using an HPLC-MS detection system, and competition with Eu(III) by monitoring equilibrium by luminescence spectroscopy. The 1:1 stability constants, log beta101, are the following: Gd, 22.06 (23.2 in 0.1 M Me4NCl); Eu, 22.21; Fe, 26.66; Ca, 10.45; Cu, 21.3; Zn, 17.82. The exchange kinetics of the Gd complex, MS-325, with the radioactive tracer (152,154)Eu were studied at 25 degrees C in 0.1 M NaClO4. The exchange reaction has acid-dependent and acid-independent terms. The rate expression is given by the following: R = k(a)[GdL][H]2 + kb[GdL][Gd][H] + kc[GdL][Gd]. The rate constants were determined to be the following: k(a) = 1.84 x 10(6) M(-2) x min(-1), kb = 2.87 x 10(3) M(-2) x min(-1), kc = 3.72 x 10(-3) M(-1) x min(-1). MS-325 is 2-3 times more stable than GdDTPA at pH 7.4 and is 10-100 times more kinetically inert.

Chelating Agents↗

PubMed1975

Contaminants in food: analytical problems and achievements.

In evaluating the toxicological significance of such contaminants as trace metals, polynuclear aromatic hydrocarbons, mycotoxins, pesticides and nitrosamines, analytical chemistry plays an important role. The detection and identification of these in various foods at the mg/kg or mug/kg levels has posed some difficult analytical problems. Considerable progress has been made in this field in the past decade, however, an opportunity is taken to review the achievements in terms of specificity and sensitivity for each class of contaminant.

Anti-Bacterial Agents↗

PubMed1979

gamma-Aminobutyric acid efflux from sympathetic glial cells: effect of 'depolarizing' agents.

1. Isolated desheathed rat superior cervical ganglia were incubated in [3H]2,3,-gamma-aminobutyric acid ([3H]GABA) solution (1--10 microM for 2--3 hr) in the presence of 10 microM-amino-oxyacetic acid (AOAA). The subsequent efflux of tritium into a stream of superfused non-radioactive GABA-free Krebs solution at 25 degrees C was measured. 2. In the presence of 10 micrometer-AOAA the mean basal efflux rate coefficient (k0) for exit of tritium into the superfusion fluid was 0.7 x 10(-3) min-1. More than 98% of effluent tritium comprised unchanged [3H]GABA. The rate coefficient showed no correlation with the amount of [3H]GABA previously accumulated by the ganglion. 3. Elevation of [K+]o to greater than 50 mM increased the rate coefficient for [3H]GABA release by up to four times. Changes in efflux rate were not correlated with osmotic changes, and persisted after re-accumulation of effluent [3H]GABA by the inward carrier was inhibited. The effect of alkali metal cations diminished in the order Rb+ greater than K+ greater than Cs+Li+. Effects of K+ solutions were not reduced by omitting Ca2+ ions, with or without the addition of Mg2+. 4. Application of electrical pulses (0.1--1 msec duration, 1--10 Hz, 4 min trains) to the ganglion soma or to the preganglionic nerve trunk also raised k0. This effect declined with repeated stimulus trains, without an accompanying diminution in the response to K+. Responses to electrical stimulation were not reduced by amethocaine (300 microM), tetrodotoxin (3 microM) or raised [Mg2+i1 (0 mM-[Ca2+]/30 mM-[Mg3+]). Separate local superfusion of the pre- and post-ganglionic nerve trunks and of the ganglion soma showed that the response to electrical stimulation was localized to the vicinity of the stimulus and was not propagated along the nerve trunks or across the synapses. 5. Electrical recording from impaled 'inexcitable' cells (presumed to be neuroglial cells (Appendix)) indicated that the quantities of K+ ion accumulating during repetitive nerve stimulation are insufficient to stimulate the release of GABA from the glial cells. No physiological role for the release process in modulating neuronal excitability could be adduced.

Aminooxyacetic Acid↗

PubMed1984

Lung cancer in Swedish iron miners exposed to low doses of radon daughters.

In a retrospective study, we investigated lung-cancer mortality from 1951 to 1976 in 1415 Swedish iron miners exposed to short-lived radioactive daughters of radon gas at concentrations leading to annual doses close to the currently accepted occupational limit. Fifty deaths from lung cancer were observed, as compared with 12.8 expected; expected rates were determined by a smoking-specific analysis based on data from a random sample of the Swedish male population. Among nonsmokers 18 deaths were observed, as compared with 1.8 expected; among current smokers and recent exsmokers 32 deaths were observed and 11.0 were expected. The effects of smoking and exposure to alpha radiation from radon daughters were nearly additive. Comparison of lung-cancer risk coefficients from this study and from other cohort studies of underground miners showed good agreement. Exposure to radon daughters is a major medical problem is underground metal mining, but our results also indicate that exposure to radon daughters at home accounts for an appreciable number of cases of lung cancer in the general population.

Adult↗

PubMed2005

A review of the potential for radium from luminising activities to migrate in the environment.

During the first half of the twentieth century, radium, mixed with other components, was used to luminise many items, including watches, clocks, dials and meters. On many sites, and in particular MoD sites, luminised instruments and paint were disposed of by burning and burial. This paper presents a review of the potential for radium from such sites to migrate in the environment. The most likely mechanisms of migration of radium from former luminising sites in the UK are surface-water erosion and transport, and the action of animals and people. Plant uptake or rainsplash followed by cropping of the plants is another possible mechanism, but the extent of impact is uncertain. The migration of significant quantities of radium through soils or rocks, or due to landsliding or wind transport, is considered to be of minimal importance to most UK sites. A low pH, high salinity (in particular of group II metals) or reducing groundwater would need to be present for migration through soils/rocks to occur and such conditions are unlikely to be present in most shallow aquifer systems in the UK. To reduce the potential for migration to occur it is recommended that luminising wastes at ground surface are removed or covered, that controls are put in place to limit animal activity and that human entry to former luminising sites is restricted.

Animals↗

PubMed1976

[Bone-seeking radioactive substances in nuclear medicine].

The concept of bone affinity of a radioactive tracer is developed on theoretical grounds and is discussed on the basis of the various substances used in nuclear medical diagnosis of bone disease. On the basis of results on the uptake of very short lived nuclides and extremely large molecules, evidence is provided that the incorporation of the tracer in the apatite crystal is not a primary criterion of bone affinity since incorporation cannot take place on timelimiting grounds in the former case and on spatial grounds in the latter. The fixation on bone is therefore more likely the result of non-specific adsorption processes. The utility of a radioactive substance in practical application in nuclear medicine depends on the radioactive characteristics of the nuclide and on its behavior in the organism. In this context the quality of the scintigram is particularly dependent on the mode and rate of elimination of that fraction of the tracer that is not bound by the skeleton. The various mechanism which cause differences in the uptake of tracer by healthy and pathological bone tissue are discussed with special regard to the role of blood flow.

Barium↗

PubMed1990

Pharmacokinetics of 99mTc-metallothionein-B72.3 and its F(ab')2 fragment.

The radionuclide of choice for use in diagnosis in most nuclear medicine diagnostic procedures is 99mTc. It is important, therefore, to establish whether there is potential clinical efficacy of an antitumor antigen directed monoclonal antibody labeled with 99mTc. We have investigated the potential use of a 99mTc labeled antibody complex which uses conjugation of the metal binding protein, metallothionein (MT), to bind the radiolabel. The stability and pharmacokinetics of the conjugates in normal and tumor bearing mice were compared to radioiodinated controls. Measurements done in CD-1 mice comparing either 99mTc-MT-B72.3 with 125I-B72.3 or 99mTc-MT-F(ab')2 with 125I-F(ab')2 indicated that the 99mTc-MT-B72.3 cleared at a rate which was faster than 125I-B72.3 while the two radiolabeled F(ab')2 fragments cleared at similar rates. The 99mTc from both labeled IgG and F(ab')2 was found in the kidneys and urine. While all the 99mTc in the urine was in the form of low molecular weight compounds, the serum contained radioactivity comigrating on size exclusion chromatography with the injected monoclonal antibody. With the exception of kidneys, organ values for 99mTc-MT-B72.3 were consistently lower than the 125I values, while the 99mTc-MT-F(ab')2 cleared other organs at similar rates to those for the iodinated monoclonal antibody. Both 99mTc-MT-B72.3 and F(ab')2 showed higher 24-h tumor:blood ratios than the iodinated proteins. Due to the pharmacokinetic properties of 99mTc-MT-F(ab')2 and the half-life of 99mTc, 99mTc-MT-F(ab')2 is the agent best suited for imaging.

Animals↗

PubMedDate not supplied

Role of mercury (Hg) in resistant infections & effective treatment of Chlamydia trachomatis and Herpes family viral infections (and potential treatment for cancer) by removing localized Hg deposits with Chinese parsley and delivering effective antibiotics using various drug uptake enhancement methods.

The authors found that antibiotics used to treat various infections often were ineffective in the presence of abnormal localized deposits of heavy metals like Hg and Pb, which were often observed to co-exist with Chlamydia trachomatis, Herpes Simplex Types I & II, Cytomegalovirus(CMV), and other micro-organisms. Our earlier research revealed that despite rigorous treatment with antibiotics together with various drug uptake enhancement techniques, subjects who had been treated for Chlamydia trachomatis infections, seemingly successfully with disappearance of their symptoms, were often experiencing recurrences within several months after completion of their treatment despite taking precautions against reinfection. Careful examination of the entire body of these symptom-free patients with the Bi-Digital O-Ring Test revealed that the Chlamydia trachomatis had retreated to 3 approximately 5 hiding places with localized increase in uric acid levels: 1) sublingual caruncle, 2) a small round area in the right and/or left axillae, 3) the genitals (Corona Glandis area of the Glans Penis at the Fossa Navicularis of the urethra in the male, and near the orifice of the urethra in the female), 4) Insulin-like Growth Factor positive horizontal lines, particularly above and below the knees, 5) the maxillary, ethmoid and frontal sinuses and the horizontal lines at the base of the nostrils (particularly small areas where Insulin-like Growth Factors exist). We found that all these areas contain Insulin-like Growth Factors I & II which are reduced in the presence of infection. Even when drug uptake of antibiotics was selectively increased in these 3 approximately 5 areas by various drug uptake enhancement methods developed by the 1st author, still the infection persisted. In the spring of 1995, use of Chinese parsley for successful elimination of Hg deposits existing in various organs of the first author as the result of the decay of radioactive Thallium 201 injected for cardiac SPECT, was accidentally discovered after eating Vietnamese soup, which happened to contain Chinese parsley, also called cilantro. We also found Chinese parsley accelerates the excretion of Hg, Pb, and A1 from the body though the urine. Our subjects were given a course of antibiotics (Doxycycline for Chlamydia trachomatis infection) or anti-viral agents (EPA with DHA for Herpes Family Viruses) together with Chinese parsley. Since these vegetable/herbs were eaten, the amount of effective substance absorbed varied and some people did not like the taste of these relatively large amounts of either cooked or raw parsley or its juice, but together with effective antibiotics delivered by drug uptake enhancement methods to the infected areas, the substances worked synergistically, rapidly reducing the generalized symptoms and infection. The micro-organisms retreated to the 3 approximately 5 areas listed above where, with continued treatment, they were significantly reduced, but not completely eliminated. Because of these problems, a pharmaceutical company was asked to produce a Chinese parsley table containing a controlled amount in a highly absorbable form. When 11 subjects were treated with Doxycycline for Chlamydia trachomatis infection, or anti-viral agents (EPA with DHA) for Herpes Family Viruses, drug uptake enhancement methods to selectively increase delivery of the drugs to the affected areas, and Chinese parsley tablets to remove the heavy metal deposits, the last traces of the infections and clinical symptoms disappeared completely. Therefore we hypothesized that the infectious micro-organisms mentioned above, somehow utilize the Hg or Pb to protect themselves from what would otherwise be effective antibiotics, and/or that heavy metal deposits in some way make antibiotics ineffective. Since the micro-organisms retreat to areas in which Insulin-like Growth Factors I & II normally exist, they may be utilizing them for their own growth and multiplication. These phenomena ma

Adult↗

PubMed1994

Carcinogenic and cocarcinogenic effects of radon and radon daughters in rats.

It has been previously established that lung cancer could be induced in rats by exposure to radon and radon daughters. Although the oat-cell carcinomas that are common in humans were not found in rats, other histological types of lung carcinomas, especially squamous cell carcinomas and primitive lung adenocarcinomas, were similar to those observed in humans. A dose-effect relationship was established for cumulative doses varying from 25 to 3000 working-level-months (WLM), which was similar for medium and high cumulative doses to that observed in uranium miners. This experimental protocol was also used to study the potential cocarcinogenic effects of other environmental or industrial airborne pollutants such as tobacco smoke, mineral fibers, diesel exhausts, or minerals from metallic mine ores that may act synergistically with radon exposure. In rats exposed to radon and tobacco smoke combined, the incidence of lung cancers was higher by a factor of 2-4 according to the cumulative radon exposure and the duration of tobacco smoke exposure. When mineral fibers were injected intrapleurally, an increased incidence of malignant thoracic tumors was observed in rats exposed to radon and fibers combined, but synergistic effects resulted in additivity. With diesel exhausts or minerals from metallic ores, a slight, nonsignificant increase in the incidence of lung carcinomas was observed compared with rats exposed to radon alone. These results demonstrated that it is possible to establish the potential cocarcinogenic action, showing either multiplicative, additive, or no effect of various environmental or industrial airborne pollutants combined with radon exposure. This radon model is valid for investigating possible interactions between two occupational exposures.

Air Pollutants↗