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Biomedical subjects

G Lunn

Publications and source records attributed to G Lunn.

35 records · Page 2Linked to original sources
PubMed1988

Decontamination and disposal of nitrosoureas and related N-nitroso compounds.

An improved procedure for chemically decontaminating residues of nitrosoureas and related N-nitroso compounds ("nitrosamides") commonly used in the cancer research laboratory is proposed. Treatment of accumulated wastes with aluminum:nickel alloy powder while progressively increasing the basicity of the medium consistently led to at least 99.98% destruction of each nitrosamide tested. Hazardous diazoalkanes were never detected in yields of greater than 0.1%. The mutagenicity of the completed reaction mixtures was never more than 3 times background except when the N-nitroso compound contained a 2-chloroethyl group. In most cases, the completeness of reaction could be determined chromatographically, not only to demonstrate the disappearance of the starting N-nitroso compound, but also to follow production of identifiable products in sufficient abundance to account for the starting material destroyed; none of the organic products observed was mutagenic in any of the four tester strains used. The procedure described herein proved reliable in two checker laboratories besides our own when applied to mixtures of seven N-nitroso compounds: N-methyl-N-nitroso-p-toluene-sulfonamide; N-methyl-N-nitrosourethane; N-methyl-N-nitrosourea; N-methyl-N'-nitro-N-nitrosoguanidine; N-ethyl-N-nitrosourea; N-ethyl-N'-nitro-N-nitrosoguanidine; and N-ethyl-N-nitrosourethane. All of the other procedures investigated for destruction of nitrosamides, including the widely used approach of dissolving the nitrosamides in alkali, were associated with important disadvantages.

Chemical Phenomena↗
PubMed1988

Dealing with spills of hazardous chemicals: some nitrosamides.

Spills of N-methyl-N-nitrosourea, N-ethyl-N-nitrosourea, N-methyl-N-nitrosourethane and N-ethyl-N-nitrosourethane can be decontaminated using a mixture of ethanol and saturated aqueous sodium bicarbonate solution. Spills of N-methyl-N-nitroso-p-toluenesulphonamide, N-methyl-N'-nitro-N-nitrosoguanidine and N-ethyl-N'-nitro-N-nitrosoguanidine can be decontaminated with a solution of sulphamic acid in 2 M-hydrochloric acid. In all cases the nitrosamides are completely destroyed and only non-mutagenic reaction mixtures are produced.

Chromatography, High Pressure Liquid↗
PubMed1988

Recommended safe practices for using the neurotoxin MPTP in animal experiments.

The metabolism and distribution of the parkinsonian syndrome inducing neurotoxin MPTP has been studied in non-human primates and mice housed in controlled environmental chambers. 14C6-MPTP was prepared and injected at concentrations normally employed for lesioning experiments (30 mg/kg in mice, 0.3 mg/kg in monkeys). All interior surfaces of the chambers which could be reached by animals or their excreta were contaminated with radiolabeled metabolites. Vapor born unmetabolized MPTP was negligible, although significant amounts of MPTP were found in the excreta of mice (less than or equal to 15% injected dose) and small amounts from rhesus monkeys (less than 2%). Procedures to minimize contact with animal fur, bedding and excreta should protect investigators working with MPTP over extended periods. Permanganate oxidation effectively detoxifies solutions of MPTP. MPTP, MPP+, common synthetic intermediates, and the products of MPTP's oxidation are not mutagenic as measured by a Salmonella-microsome assay.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Ethidium bromide: destruction and decontamination of solutions.

Ethidium bromide in water, TBE buffer, Mops buffer, and cesium chloride solution may be completely degraded by reaction with sodium nitrite and hypophosphorous acid. Only non-mutagenic reaction mixtures were produced. Destruction was greater than 99.8% in all cases; the limit of detection was 0.5 micrograms ethidium bromide per milliliter of solution. Ethidium bromide also may be removed completely from the above solutions by using Amberlite XAD-16 resin. The limit of detection was 0.05 micrograms ethidium bromide per milliliter of solution (0.27 micrograms/ml when cesium chloride solution was used).

Decontamination↗
PubMed1987

Reductive destruction of dacarbazine, procarbazine hydrochloride, isoniazid, and iproniazid.

Reductive destruction of dacarbazine, procarbazine hydrochloride, isoniazid, and iproniazid using nickel-aluminum alloy in basic solution is described. Solutions of dacarbazine 10 mg/mL were prepared by adding dacarbazine 100 mg, citric acid 100 mg, and mannitol 50 mg to 10 mL of water. Aqueous solutions of procarbazine hydrochloride 10 mg/mL were prepared from commercially available capsules, and aqueous solutions of isoniazid 10 mg/mL and iproniazid 5 mg/mL were prepared from powdered drug. Reductive destruction of drugs was accomplished by mixing each solution with an equal volume of 1 M potassium hydroxide solution and adding 1 g of nickel-aluminum alloy for each 20 mL of basified solution. The resulting mixtures were stirred for 20 hours (96 hours for iproniazid) and analyzed by high-performance liquid chromatography and gas chromatography for the presence of residual drug and degradation products. Dacarbazine solutions were also subjected to destruction by photolysis and by oxidation using potassium permanganate in sulfuric acid, and the results were compared with those obtained by reductive destruction. All reaction mixtures were tested for mutagenicity in Salmonella strains. All drugs subjected to reductive destruction were completely degraded to the limits of detection of the assay and produced only nonmutagenic reaction mixtures. The only acceptable results for dacarbazine were obtained by the reductive destruction method. Reduction of dacarbazine, procarbazine hydrochloride, isoniazid, and iproniazid with nickel-aluminum alloy in dilute base appears to be a good method for the destruction of these toxic compounds.

Alloys↗
PubMed1986

Oxidative destruction of hydrazines produces N-nitrosamines and other mutagenic species.

As part of the joint International Agency for Research on Cancer-National Cancer Institute program for the evaluation and development of methods for the degradation of chemical carcinogens, four oxidative techniques for the degradation of hydrazines were investigated. The oxidizing agents used were as follows: sodium hypochlorite, calcium hypochlorite, potassium iodate, and potassium permanganate in sulfuric acid. In each case, at least 99% of the hydrazine initially present was destroyed; however, the potential usefulness of these methods was compromised by the formation (in some reaction mixtures) of carcinogenic N-nitroso compounds and/or unknown mutagenic species. Oxidative degradation of hydrazines is recommended only for the decontamination of glassware and for the treatment of spills, for which reductive degradation methods are not suitable.

Animals↗
PubMed1986

Effects of altering the ATP/ADP ratio on pump-mediated Na/K and Na/Na exchanges in resealed human red blood cell ghosts.

Resealed human red blood cell ghosts were prepared to contain a range of ADP concentrations at fixed ATP concentrations and vice versa. ATP/ADP ratios ranging from approximately 0.2 to 50 were set and maintained (for up to 45 min) in this system. ATP and ADP concentrations were controlled by the addition of either a phosphoarginine- or phosphocreatine-based regenerating system. Ouabain-sensitive unidirectional Na efflux was determined in the presence and absence of 15 mM external K as a function of the nucleotide composition. Na/K exchange was found to increase to saturation with ATP (K 1/2 approximately equal to 250 microM), whereas Na/Na exchange (measured in K-free solutions) was a saturating function of ADP (K 1/2 approximately equal to 350 microM). The elevation of ATP from approximately 100 to 1,800 microM did not appreciably affect Na/Na exchange. In the presence of external Na and a saturating concentration of external K, increasing the ADP concentration at constant ATP was found to decrease ouabain-sensitive Na/K exchange. The decreased Na/K exchange that still remained when the ADP/ATP ratio was high was stimulated by removal of external Na. Assuming that under normal substrate conditions the reaction cycle of the Na/K pump is rate-limited by the conformational change associated with the release of occluded K [E2 X (K) X ATP----E1 X ATP + K], increasing ADP inhibits the rate of these transformations by competition with ATP for the E2(K) form. A less likely alternative is that inhibition is due to competition with ATP at the high-affinity site (E1). The acceleration of the Na/K pump that occurs upon removing external Na at high levels of ADP evidently results from a shift in the forward direction of the transformation of the intermediates involved with the release of occluded Na from E1P X (Na). Thus, the nucleotide composition and the Na gradient can modulate the rate at which the Na/K pump operates.

Adenosine Diphosphate↗
PubMed1985

Destruction of cyanogen bromide and inorganic cyanides.

Cyanogen bromide in water and seven organic solvents and sodium cyanide in water may safely and efficiently (greater than 99.7%) be destroyed using sodium hydroxide (1 M) solution and commercially available sodium or calcium hypochlorite. Details are given of an analytical procedure which can be used to check the final reaction mixture for the presence of residual cyanogen bromide or cyanide.

Calcium↗
PubMed1985

Validation of techniques for the destruction of dimethyl sulfate.

It has been reported that dimethyl sulfate (DMS) can be degraded with sodium hydroxide solution (1 mol/L), sodium carbonate solution (1 mol/L), or ammonium hydroxide solution (1.5 mol/L). This has now been confirmed. Complete destruction of undiluted DMS or DMS in solvents miscible with water (methanol, ethanol, DMSO, DMF, acetone) or solvents partially miscible or immiscible with water (toluene, p-xylene, benzene, 1-pentanol, ethyl acetate, chloroform, carbon tetrachloride, acetonitrile) could be obtained using any of the above methods. Reaction times were 15 min after homogeneity was obtained for undiluted DMS, 15 min for solutions in methanol, ethanol, DMSO, and DMF, one hour for solutions in acetone, three hours for acetonitrile, and one day for the other solvents listed above. The final reaction mixtures were tested for mutagenicity, and when the solutions were not cytotoxic, no mutagenic response was obtained. DMS in solution was determined by a colorimetric method. The products of the reactions were found to be methanol when NaOH and Na2CO3 were used and methylamine, dimethylamine, trimethylamine, and methanol when ammonium hydroxide was used. The stability of DMS in various solvents was also determined.

Animals↗
PubMed1984

Destruction of carcinogenic and mutagenic N-nitrosamides in laboratory wastes.

The chemical degradation of five N-nitrosamides used widely for the experimental induction of cancer has been studied with the goal of identifying, and experimentally validating, reliable methods that can be recommended for the destruction of carcinogenic N-nitrosoureas and related compounds in laboratory wastes. Although data are not yet complete, preliminary evidence indicates that none of the five methods studied thus far is ideal for hazard-control purposes. Decomposition with 1 mol/L potassium hydroxide solution destroyed the N-nitrosamides, but generated diazoalkanes, which are carcinogenic, toxic and potentially explosive. Treatment with strong acid in the presence of sulfamic acid or iron filings completely decomposed all N-nitrosamides without forming diazoalkanes, but failed in the presence of solvents which were immiscible with water. Cleavage with hydrogen bromide in glacial acetic acid proceeded to a point of maximum degradation, following which gradual reformation of the N-nitrosamide was observed; this resynthesis could be avoided by carefully bubbling nitrogen through the reaction mixture, but degradation was slow or failed completely in the presence of hydroxylic solvents. Permanganate oxidation was effective in sulfuric acid solution, but was incomplete when an alcohol or dimethyl sulfoxide was present. Salmonella typhimurium tester strains TA1535, TA1530 and TA100, which detect base-pair substitutions in DNA, detected mutagenic degradation products in each of the destruction methods, with the exception of the hydrobromic acid/acetic acid procedure.

Carcinogens↗
PubMed1983

Safe disposal of carcinogenic nitrosamines.

A simple one-step procedure for chemically degrading nitrosamine residues generated in the research laboratory is described. Treatment with aluminum-nickel alloy powder and aqueous alkali rapidly reduced all 11 nitrosamines studied to the corresponding amines. Hydrazines were produced as transitory intermediates, but these potential carcinogens were also easily reduced under the conditions employed, and no products except amines, ammonia, and, in some cases, alcohols were detected in the final reaction mixtures. Reduction proceeded smoothly in every other solvent system tested, except that reactions in acetone or dichloromethane solution were sometimes slow, incomplete, and/or led to unidentified products; therefore, we cannot recommend the procedure for use in these solvents. Otherwise, the method was efficient, reliable, and inexpensive and has been recommended as one of the preferred means of degrading potentially carcinogenic nitrosamines to innocuous products. Details of its application to some decontamination and disposal problems commonly encountered in the research laboratory are provided. Data illustrating this procedure's advantages over six other reducing systems are also presented.

Chemical Phenomena↗
PubMed1979

Transport accounts for glutathione turnover in human erythrocytes.

Human erythrocytes were incubated with 3H-glycine to label the glutathione pool. These cells were then used to determine the rate of oxidized glutathione (GSSG) transport out of erythrocytes. For 6 normal individuals, the mean transport rate was 6.7 nmole GSSG/hr/ml red cells. This transport rate would suggest a half-life of 4.7 days for the erythrocytic glutathione, which is in close agreemwnt with the observed in vivo half-life of 4 days. These data demonstrate that GSSG transport can account for the observed turnover of erythrocytic glutathione.

Biological Transport↗
PubMed1977

Accelerating effect of 2,4,6-trinitrophenol on the glycolytic rate of human red cells.

A number of instantaneous changes occurred when picrate was added to a suspension of human red cells in steady state with respect to glycolysis and ion distribution across the membrane at pH 7.40. The rate of glycolysis increased, without change in glycolytic quotient, to a new steady-state value, the effect reaching a maximum of 1.75 times the rate of the control at 0.5 mM picrate. Inorganic phosphate (P(i)) was released at a relatively constant rate, increasing with picrate concentration to 1.0 mmol P(i)/liter cells x h at 5-6 mM picrate. The steady- state concentrations of ATP and 1,3-diphosphoglycerate (1,3-DPG) decreased to new stable values within 15-45 min after the addition of picrate. The ATP level was affected only at picrate concentrations of 1 mM or more, and the level of ATP stabilized at 75 percent of the control values at 4 mM of picrate. In contrast, 1,3-DPG concentrations decreased to 40 percent of the control value of 0.5 mM picrate. Higher concentrations of picrate resulted in only a small additional decrease in the stationary concentration of 1,3-DGP. A net efflux of cellular potassium at constant rate took place. This net efflux was an almost linear function of picrate concentration in the range of 0.1-3 mM. At the latter concentration the net efflux amounted to about 2.7 meq/liter cells x h and a further increase in picrate concentration caused only a minor increase in the potassium efflux. Possible mechanisms for the effects of picrate on human red cell glycolysis are discussed.

Adenosine Diphosphate↗
PubMedDate not supplied

Observations on the effect of immersion in Bath spa water.

Immersion in water in spas has been practised for centuries and has many proponents. Despite fierce debate about its efficacy there has been little scientific evaluation of the effect of immersion in mineral waters. Eight normal subjects were immersed in Bath spa water for two hours and the renal, haematological, and cardiovascular responses were compared with those in the control periods before and after immersion. Significant, twofold diuresis and natriuresis, 5% haemodilution, and a 50% increase in cardiac index were observed in subjects immersed, sitting, in Bath spa water at 35 degrees C. These changes may constitute part of the scientific rationale for spa treatment in many states of disease.

Adult↗