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Biomedical subjects

H F Mower

Publications and source records attributed to H F Mower.

At least 19 recordsLinked to original sources
PubMed2000

Formation of N-nitrosamines and N-nitramines by the reaction of secondary amines with peroxynitrite and other reactive nitrogen species: comparison with nitrotyrosine formation.

Reactive nitrogen species, including nitrogen oxides (N(2)O(3) and N(2)O(4)), peroxynitrite (ONOO(-)), and nitryl chloride (NO(2)Cl), have been implicated as causes of inflammation and cancer. We studied reactions of secondary amines with peroxynitrite and found that both N-nitrosamines and N-nitramines were formed. Morpholine was more easily nitrosated by peroxynitrite at alkaline pH than at neutral pH, whereas its nitration by peroxynitrite was optimal at pH 8.5. The yield of nitrosomorpholine in this reaction was 3 times higher than that of nitromorpholine at alkaline pH, whereas 2 times more nitromorpholine than nitrosomorpholine was formed at pH <7.5. For the morpholine-peroxynitrite reaction, nitration was enhanced by low concentrations of bicarbonate, but was inhibited by excess bicarbonate. Nitrosation was inhibited by excess bicarbonate. On this basis, we propose a free radical mechanism, involving one-electron oxidation by peroxynitrite of secondary amines to form amino radicals (R(2)N(*)), which react with nitric oxide ((*)NO) or nitrogen dioxide ((*)NO(2)) to yield nitroso and nitro secondary amines, respectively. Reaction of morpholine with NO(*) and superoxide anion (O(2)(*)(-)), which were concomitantly produced from spermine NONOate and by the xanthine oxidase systems, respectively, also yielded nitromorpholine, but its yield was <1% of that of nitrosomorpholine. NO(*) alone increased the extent of nitrosomorpholine formation in a dose-dependent manner, and concomitant production of O(2)(*)(-) inhibited its formation. Reactions of morpholine with nitrite plus HOCl or nitrite plus H(2)O(2), with or without addition of myeloperoxidase or horseradish peroxidase, also yielded nitration and nitrosation products, in yields that depended on the reactants. Tyrosine was nitrated easily by synthetic peroxynitrite, by NaNO(2) plus H(2)O(2) with myeloperoxidase, and by NaNO(2) plus H(2)O(2) under acidic conditions. Nitrated secondary amines, e.g., N-nitroproline, could be identified as specific markers for endogenous nitration mediated by reactive nitrogen species.

Aniline Compounds↗
PubMed1999

Analysis of 3-nitrotyrosine in biological fluids and protein hydrolyzates by high-performance liquid chromatography using a postseparation, on-line reduction column and electrochemical detection: results with various nitrating agents.

Nitric oxide reacts rapidly with superoxide to form the strong nitrating agent peroxynitrite, which is responsible for much of the tissue damage associated with diverse pathophysiological conditions such as inflammation. The occurrence of free or protein-bound nitrotyrosine (NTYR) has been considered as evidence for in vivo formation of peroxynitrite. However, various agents can nitrate tyrosine, and their relative significance in vivo has not been determined due to lack of a sensitive method to analyze NTYR in tissue proteins and biological fluids. We have developed a new HPLC-electrochemical detection method to analyze NTYR in protein hydrolyzates or biological fluids. The sample is injected directly into a reversed-phase HPLC column and NTYR is subsequently reduced by a platinum column to 3-aminotyrosine, which is quantified with an electrochemical detector. The method is simple, selective, and sensitive (detection limit, 0.1 pmol per 20-microl injection). We have applied this method to compare in vitro the ability of various nitrating agents to form NTYR in bovine serum albumin and human plasma. Yields of NTYR formed in human plasma proteins incubated with 1 or 10 mM nitrating agent decreased in the following order: synthetic peroxynitrite > 3-morpholinosydonimine, a generator of both NO and superoxide > Angeli's salt, which forms nitroxyl anion (NO-) > spermine-NONOate, which releases NO > sodium nitrite plus hypochlorite, which forms the nitrating agent nitryl chloride (NO2Cl). A simple purification method using a C18 Sep-Pak cartridge is also described for analysis of free NTYR in human plasma.

Chromatography, High Pressure Liquid↗
PubMed1995

Anti-microbial activity and anti-complement activity of extracts obtained from selected Hawaiian medicinal plants.

Selected plants having a history of use in Polynesian traditional medicine for the treatment of infectious disease were investigated for anti-viral, anti-fungal and anti-bacterial activity in vitro. Extracts from Scaevola sericea, Psychotria hawaiiensis, Pipturus albidus and Eugenia malaccensis showed selective anti-viral activity against Herpes Simplex Virus-1 and 2 and Vesicular Stomatitis Virus. Aleurites moluccana extracts showed anti-bacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa, while Pipturus albidus and Eugenia malaccensis extracts showed growth inhibition of Staphylococcus aureus and Streptococcus pyogenes. Psychotria hawaiiensis and Solanum niger inhibited growth of the fungi Microsporum canis, Trichophyton rubrum and Epidermophyton floccosum, while Ipomoea sp., Pipturus albidus, Scaevola sericea, Eugenia malaccensis, Piper methysticum, Barringtonia asiatica and Adansonia digitata extracts showed anti-fungal activity to a lesser extent. Eugenia malaccensis was also found to inhibit the classical pathway of complement suggesting that an immunological basis for its in vivo activity was identified. This study has confirmed some of the ethnobotanical reports of Hawaiian medicinal plants having curative properties against infections using biological assays in vitro.

Anti-Bacterial Agents↗
PubMed1995

Detection of mutagen specific adduct formation in DNA using sequencing methodology.

It has been reported that single stranded viral DNA reacts with the carcinogen, chloroacetaldehyde at specific hot spots (Premaratne et al., 1993 Int. J. Biochem. 25, 1669-1672). We tested this occurrence with several other mutagens and potential carcinogens. A series of chemicals (chloroacetaldehyde, methyl, ethyl, and propyl nitro nitrosoguanidine, hydrazine, 2,4 dinitrophenyl hydrazine, hydroxylamine and methyl methanesulfonate) were each separately reacted with viral M13mp18 DNA for 2 hr at 37 degrees C and pH 4.9. The locations of adduction were identified as points of chain termination (or polymerase fall off) when the reacted DNA was subjected to a modified sequencing procedure that had ample regular labeled and unlabeled nucleotides but lacked dideoxy chain termination mixtures. Chain termination was observed to occur at specific, non-random, sites rather than with equal probability at all bases of the DNA. Chemicals with similar structures had identical points of "fall off". The pattern of chain termination appears to be unique to each class of compounds and is independent of temperature, pH, and salt concentration. Termination is believed to occur when the DNA polymerase encounters an adduct. Mutagens of different unrelated structures when reacted with this DNA produced different sites of adduct formation, while the alkyl nitro nitrosoguanidines, compounds with homologous structure showed identical points of chain termination.

Animals↗
PubMed1994

Detection of small quantities of double stranded DNA by enhanced fluorescence of substituted aldehyde modified polydeoxynucleotide-ethidium bromide complexes.

A method for the detection of small amounts of double stranded DNA by a simple incubation procedure involving the reaction of the nucleotide bases in DNA with chloroacetaldehyde is described. Following incubation, the presence of DNA may be visualized by the orange fluorescence emitted when ethidium bromide (EtBr) is added. Alternatively, the aldehyde/DNA mixture may be separated by agarose gel electrophoresis and individual double stranded DNA visualized by exposing the gel to ethidium bromide and observing the orange ultraviolet light induced fluorescence of the aldehyde modified double stranded ethidium bromide complex (Waring, M.J. (1965) J. Mol. Biol. 13, 269-282). At least a 20-fold increase in the detection of double stranded DNA is possible by this procedure. An important aspect of this method is that the visualization of single stranded DNA is not enhanced.

Acetaldehyde↗
PubMed1994

Enhanced mutagenic effect of a 60 Hz time-varying magnetic field on numbers of azide-induced TA100 revertant colonies.

Forty-eight hours exposure to a two Gauss (0.2 mT) rms 60 Hz time varying sinusoidal electromagnetic field increased the number of azide induced TA100 revertant colonies of Salmonella typhimurium 14% as compared with controls in the ambient < 2 milli-Gauss 60 Hz field. In the absence of the electromagnetic field, the numbers of mutant colonies grown within and outside the non-energized coil were nearly identical. Without azide, the number of "spontaneous" mutant colonies forming in the experimental field was not statistically significant from numbers of colonies not exposed to field effects. Experimental temperature variation of 2 degrees C had little effect on colony formation, and the enhanced production of revertant colonies in the presence of the magnetic field was maintained during continued culture for 5 additional days.

Azides↗
PubMed1993

Identification of DNA adducts at specific locations by sequencing techniques.

1. A simple procedure for the accurate identification of the positions of adduct formation when viral M13mp18 single stranded DNA is treated with chloroacetaldehyde (CAA) is presented. 2. The normal dideoxy sequencing reaction protocol was employed except no dideoxy nucleotides were used to cause chain termination. 3. Instead, the CAA adducted bases of the template DNA act as points of polymerase fall off causing the appearance of bands of DNA sequencing gel autoradiographs marking locations where adduct formation may have occurred.

Acetaldehyde↗
PubMed1992

Mutagenicity of nitric oxide and its inhibition by antioxidants.

Nitric oxide (NO) is produced both by macrophages in vivo as a physiological response to infection and by a variety of cell types as an intercellular messenger. In addition, NO and nitrogen dioxide (NO2) are significant components of many combustion processes. The ubiquitous exposure of humans to nitrogen oxides (NOx), both endogenously and exogenously, may play a significant role in the carcinogenic process due to nitrosation of amines by NOx. We report here that exposure to low concentrations of NO, alone or in combination with NO2, results in significantly enhanced mutation in Salmonella typhimurium TA1535 using a modified Ames Salmonella reversion assay. The observed mutagenicity requires that the bacteria be actively dividing at the time of exposure to NO or NO2, suggesting that the nitrogen oxides, or their reaction products, function as direct-acting mutagens and that the induced lesion is easily repairable by non-dividing cells. Exposure to NO resulted in a time- and dose-dependent increase in the number of revertants approximately proportional to the square of the NO concentration from 0 to 20 ppm. NO was a more effective mutagen relative to NO2, however, the observed requirement for O2 suggests limited oxidation of NO (presumably to NO2) is necessary. Numerous lipid- and aqueous-phase inhibitors of nitrosation, as well as a number of other general antioxidants and free-radical trapping agents, were examined for their effectiveness in blocking the mutagenic effects of NO. The mutagenic activity of NO was most effectively inhibited by beta-carotene and tocopherols. BHT, dimethyl sulfoxide and mannitol also blocked the mutagenic effects of NOx but appeared less effective than beta-carotene or vitamin E, while ascorbate was ineffective as an inhibitor of mutation resulting from NO exposure.

Antioxidants↗
PubMed1990

Formation of mutagens during the frying of Hawaiian fish: correlation with creatine and creatinine content.

Compounds mutagenic toward Salmonella typhimurium strain TA98 in the presence of rat-liver homogenates (S9) were formed when fish flesh was fried at 199 degrees C. Three species of Hawaiian fish commonly consumed in Hawaii (skipjack tuna, Katsuwonus pelamis; yellowfin tuna, Neothunnus macropterus; and milkfish, Chanos chanos) were cooked in an electric skillet, along with samples of sole (Microstomus pacificus). Organic extracts of the fish were tested in the Ames Salmonella mutagenic assay using tester strain TA98 and S9. Basic organic extracts of fried, but not raw, samples exhibited significant mutagenicity. The levels of mutagenicity were also higher among the red flesh Hawaiian fish ('ahi, aku and awa) than with the white flesh sole. Creatine and creatinine contents were highest in the Hawaiian fish and lower in the sole. Creatine levels in the fish were 50-100 times greater than the creatinine content and varied from a high of 645 mg/100 g wet weight of fish for yellowfin tuna to a low value of 251 mg/100 g for sole. Mutagen levels are only approximately related to creatine/creatinine levels suggesting that other components contained in these fish may be as important as the guanidines in determining the levels of mutagen in the cooked fish.

Animals↗
PubMed1990

Synthesis, characterization and mutagenicity of 2-nitroso-6,7-dimethoxytetrahydroisoquinoline.

The compound 6,7-dimethoxytetrahydroisoquinoline (Scheme 2, (ii] reacts with nitrous acid at ambient temperature and pH approximately 3.0 to give, in high yield the expected 2-nitroso-6,7-dimethoxytetrahydroisoquinoline (Scheme 2, (iii)). An unequivocal chemical structure of this nitroso derivative was established by high resolution mass spectrometry and 1H NMR spectrometry. Unlike many N-nitroso compounds, (iii) crystallizes in a single rotational isomer which spontaneously forms, in dimethylsulfoxide (DMSO) solution, an equilibrium mixture of the two E/Z isomeric forms with a t1/2 approximately 53 h. The compound is mutagenic to Salmonella tester strains TA98, TA100, TA1538, TA1535, and TA1537 but only in the presence of induced rat liver microsomes. The highest mutagenic activity of approximately 10 net revertants/nM was obtained with TA100 at a dose of 10 micrograms/plate. The compound (ii) is a close structural analog to the tetrahydroisoquinolines formed by endogenous condensation/cyclization reactions that can occur, between acetaldehyde and dopamine or norepinephrine, when alcohol is consumed.

Animals↗
PubMed1989

Characterization and mutagenicity of 1-nitrosotryptophol and 6-nitrotryptophol possible genotoxic substances associated with smoking and alcohol consumption.

Tryptophol (Typ) is a minor product of tryptophane metabolism in humans which is increased with alcohol consumption. Typ can react rapidly with nitrite at pH 3.0 to form 1-nitrosotryptophol (NO-Typ) in high yield. This product is also formed in various organic solvents by the reaction of NO/NO2 mixtures with Typ. Under similar conditions, NO2 in the absence of NO will react with Typ to form 6-nitrotryptophol (NO2-Typ). Both products, NO-Typ and NO2-Typ, are mutagenic when tested in the absence of rat liver microsomes with a variety of Salmonella typhimurium tester strains.

Alcohol Drinking↗
PubMed1989

Free radical scavenging activity of papaya juice.

Papaya juice is an efficient scavenger of highly reactive hydroxyl radicals (OH.) formed during 60Co irradiation of water. The OH. radicals were detected by the electron spin resonance (ESR) technique of spin trapping using DMPO (5,5-dimethyl-1-pyrroline-N-oxide) or by a colorimetric assay in which salicylate is converted into polyhydroxybenzoic acids. Papaya juice is also able to quench the ESR signal of a stable free radical (TEMPOL) and the ESR signal of the DMPO-OH adduct. The active substance(s) in papaya juice are heat-stable, dialyzable, and soluble in water but not in lipid solvents. The active agents do not appear to be ascorbate, tocopherol, or carotenoids.

Cyclic N-Oxides↗
PubMed1985

Fecal mutagenicity arising from ingestion of fried ground beef in the human.

Fried ground beef has been shown to contain mutagens, and the major mutagenic component has been identified as 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). Mutagens in feces of 3 adult volunteers were fractionated by treatment of the feces with blue cotton followed by chromatography on a carboxymethyl cellulose column. The chromatographic fraction, corresponding to MeIQx in terms of the position of elution, was examined for mutagenicity in S. typhimurium TA98 with metabolic activation. When meals containing no heated meat were eaten, this fraction of feces showed little or no mutagenicity. On eating fried ground beef, the feces excreted in the next two days showed greatly increased mutagenicity in this fraction. By eating no-meat meal subsequent to the meat meal, the mutagenicity resumed the original low level on the fourth day after the meat meal. The components in the mutagenic fraction were probably metabolites of the mutagens present in cooked meat, since analysis by high pressure liquid chromatography of the mutagenic fraction showed that the active components in the feces were different from the mutagens in cooked meat.

Animals↗
PubMed1983

Fecal neutral steroids in two Japanese populations with different colon cancer risks.

Several workers have associated fecal neutral steroids with colon cancer frequency. They suggested that the risk for colon cancer increases with a rise in the level of total and certain neutral steroids. The Japanese in Hawaii, who are at high risk for this cancer, had a higher concentration of cholesterol and total animal steroids in their fecal specimens than did the people in Akita, Japan, who are at low risk. However, the rest of the findings on neutral steroids were unremarkable or inconsistent in comparison with those of other studies. These data are suggestive but not strongly supportive of a relationship between fecal neutral steroid patterns and colon cancer risk.

Colonic Neoplasms↗
PubMed1982

Fecal mutagens in two Japanese populations with different colon cancer risks.

Human feces from 223 Japanese in Hawaii at high risk for colon cancer and feces from 166 Japanese of northern rural Japan at low risk for colon cancer were shown to contain mutagenic activity under five different test conditions. The first assay, using the Ames TA98 and TA100 Salmonella test, detected ether-soluble mutagens in the presence and absence of rat liver microsomes. Of these, the TA98 direct-acting mutagens are present more frequently in the feces of the high-risk population than the low-risk population at a high level of statistical significance (p less than 0.01). TA98 mutagens activated by rat liver microsomes also occur significantly more frequently in the feces of the Japanese from Hawaii (p less than 0.05). Mutagens detected by TA100 in the presence and absence of rat liver microsomes are not commonly found in either Japanese population. The second bacterial test system used to detect fecal mutagens uses Escherichia coli rec-. This system detects water-soluble fecal mutagens which are also present more frequently in the high-risk population than in the low-risk population (p less than 0.05).

Age Factors↗
PubMed1981

Mutagenicity of nitrosated cimetidines.

Dinitrosocimetidine and mononitrosocimetidine were tested in a series of short term assay systems. Both compounds were mutagenic in the absence of rat liver microsomes. The dinitrosocimetidine produced higher mutagenic or clastogenic effects at concentrations that were 50 to 500 times lower than the concentrations at which the mononitrosocimetidine produces its maximum effects. The most sensitive short term assay system was the Chinese hamster ovary cell culture system. Dinitrosocimetidine caused sister chromatid exchanges at a concentration of 10(-8) M and chromosome aberrations at 10(-7) M in this system. Dinitrosocimetidine had moderate activity in the bacterial short term assay systems. In the Ames test, strain TA 100 was the most sensitive. The compound was of lower activity in the E. coli WP-2 and the E. coli rec- systems.

Animals↗