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Biomedical subjects

W S Barnes

Publications and source records attributed to W S Barnes.

At least 55 records · Page 3Linked to original sources

Multipotential carcinogenicity of the fried food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline in rats.

The carcinogenicity of the mutagenic compound 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ), identified in fried and broiled foods, was investigated in female Sprague-Dawley rats. Administration by gavage of IQ (0.4 mmol/kg body weight) on a weekly regimen for 31 weeks starting with 6-week-old animals induced a high yield of multiple mammary gland carcinomas in a limited bioassay lasting a total of 52 weeks. In a positive control group receiving 4-aminobiphenyl (4-AB), the expected carcinomas in the mammary gland developed. IQ, but not 4-AB, also yielded neoplasms in the ear duct and to a lesser degree, in the liver, pancreas, and urinary bladder. In addition, with IQ, a high incidence of preneoplastic lesions in the pancreas was observed. Vehicle and untreated controls did not have any lesions. These findings demonstrate that IQ is a powerful multipotent carcinogen in the rat.

Animals↗

Effects of localized hyper- and hypothermia on maximal isometric grip strength.

Twenty-four male college students were divided into two groups and served as subjects for a study which investigated the progressive effects of heat and cold on maximum isometric grip strength. One group of 12 subjects was exposed to a heating (40 degrees C) treatment, the other to a cooling (10 degrees C) treatment. Maximum isometric grip strength was measured prior to the application of treatments and again every two minutes until the end of the 30 minute treatment period. Cutaneous temperature of the contracting limb was also measured simultaneously with the maximum contractions. With cooling, cutaneous temperature was found to decrease 16.29 degrees C by the end of the treatment period. Maximum grip strength improved 8.29 percent immediately following the application of cold and then declined 14.05 percent by the end of treatment. Heating produced a 5.96 degrees C increase in cutaneous temperature, with maximum grip strength declining 17.93 percent during the first 22 minutes of treatment. This trend then reversed itself and maximum strength improved to within 91.93 percent of the pre-treatment value. The results suggest a neural, as well as mechanical, influence of temperature on muscular contractions.

Adult↗

Biochemical mechanisms on species differences in gastric carcinogenesis.

The biochemical denitrosation of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in tissues from four strains of rat, inbred Buffalo, Lewis, B-N, and the random-bred Sprague-Dawley, with different sensitivities to MNNG-induced gastric carcinomas was investigated as a possible explanation for the species/strain differences in MNNG-induced carcinogenesis. An analytical HPLC method was developed to assay denitrosation of MNNG to N-methyl-N'-nitroguanidine (MNG) by cytosolic, microsomal, mitochondrial, and nuclear cell fractions. All the activity was contained in the microsomal and cytosolic fractions, with the major portion occurring in the cytosol. The activity in both fractions was NADPH-dependent, but denitrosation was not reduced by inhibitors of the cytochrome P-450 system. Denitrosation of MNNG post-mitochondrial supernatant (S9) fractions from liver, glandular stomach mucosa, and duodenal mucosa of the four rat strains was determined. In all strains, denitrosation activities were highest in liver. Comparisons between the three strains most sensitive to MNNG-induced gastric carcinogenesis indicated no large differences for any tissue. However, Buffalo, the most resistant strain, did have a higher level of denitrosating activity in all three tissues, which is consistent with the hypothesis that higher levels of detoxifying enzymes may lead to a decreased incidence of tumors. On the other hand, denitrosation accounts for less than 3% of the MNNG that disappears during the incubation period so that the relevance of denitrosation as a mechanism in strain-specific sensitivity to MNNG-induced gastric carcinoma requires additional studies.

Analysis of Variance↗

Formation of mutagens in cooked foods. VI. Modulation of mutagen formation by iron and ethylenediaminetetracetic acid (EDTA) in fried beef.

Mutagen formation during frying of beef is inhibited by the heavy metal chelator ethylenediaminetetracetic acid (EDTA). The addition of 1% EDTA prior to cooking reduces the mutagenicity of the basic extracts to about 60% of control values. The addition of iron as ferrous chloride or ferric chloride at 10 ppm (approximately 50% of endogenous concentrations) doubles the mutagenic activity of beef extracts. Iron, which can be released by denaturation of heme protein, therefore, can modulate the formation of mutagens in beef during cooking.

Animals↗

Respiratory capacity of developing chick red and white skeletal muscle.

Oxygen consumption, cytochrome oxidase and succinoxidase activity was measured in samples of leg and breast muscle from chick embryos ranging in age from 11 to 19 days. Respiratory parameters increased significantly in both muscle groups during embryonic life. By the later stages of incubation, leg and breast muscles differed significantly in cytochrome and succinoxidase activity. Oxygen uptake between leg and breast muscles did not differ significantly during later development. The results suggest at least a partial pre-natal differentiation of skeletal muscle in the domestic fowl.

Animals↗

Bile acids, but not neutral sterols, are tumor promoters in the colon in man and in rodents.

Analysis of the etiologic factors and relevant mechanisms involved in carcinogenesis leads to a classification of agents involved in the carcinogenic process as genotoxic or epigenetic. Their mode of action is distinct, especially with regard to dose-response effects and reversibility. The genotoxic carcinogens for colon cancer are unknown, but mutagenic components found in fried beef and fish are under study. Epigenetic agents as promoting factors play a major role in the development of cancer of the colon. Specific nutritional elements associated with colon cancer risk are high fat diets, high cholesterol intake, and low fiber intake. The role of micronutrients as modulators and inhibitors needs to be explored. Through metabolic studies in diverse populations and in reliable animal models, it is now clear that dietary fat and cholesterol control the total flow of bile acids in lumen and a high-fat, high-cholesterol diet increases the total of bile acids in the gut. Bile acids but not neutral sterols have promoting effects and are related to colon cancer risk although bile acids by themselves do not act as complete carcinogens. The effect of dietary fiber such as cereal bran is to increase stool bulk which dilutes the concentration of bile acids. Reducing the concentration of bile acids either by lower dietary fat and cholesterol or by increasing dietary fiber may effectively lower the risk for colon cancer.

Animals↗

In vitro binding of the food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline to dietary fibers.

The ability of three kinds of fiber to bind to 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a potent bacterial mutagen formed during the cooking of meat, was investigated to determine interactions among important food components. At pH 6.5 corn bran, wheat bran, and alfalfa meal each bound approximately 50% of the available IQ after incubation for 1 hour. Binding was pH-dependent, occurred optimally between pH 4 and 6, and was probably due to a cation-exchange mechanism. The pH at which IQ is efficiently bound to fiber overlaps the range of pH in the human gastrointestinal tract.

Chemical Phenomena↗

Isokinetic fatigue curves at different contractile velocities.

Twenty-five male volunteers were tested isokinetically for knee extension fatigability. A series of 10 maximal knee extensions were performed at 4 different contractile velocities: 60 degrees, 150 degrees, and 300 degrees/sec. Isokinetic fatigue curves were plotted for each of the test conditions. The degradation of torque values was expressed as a percentage of each subject's maximum torque value at that particular contractile speed. The results of the investigation indicate that (1) the isokinetic fatigue curve for knee extension appears to be linear during the initial stages of the fatiguing process; and (2) fatigue curves for knee extension appear to be identical regardless of the contractile velocity selected for investigation.

Adult↗

The relationship of Motor-unit activation to isokinetic muscular contraction at different contractile velocities.

This investigation was designed to examine 1) the relationship between motor-unit activation (as recorded by integrated EMG) and speed of contraction and 2) the relationship between mechanical work, power output, peak torque, average torque, and both velocity of movement and integrated electromyographic recordings in the elbow flexor muscles. A series of isokinetic contractions of the elbow flexor muscles was performed by six normal subjects over a range of contractile velocities. Integrated electromyographic discharge and mechanical torque were recorded simultaneously. The results of an analysis of variance, corrected for repeated measures, indicated that both torque and motor-unit electrical activity decreased as contractile velocity increased. The relationship between torque and integrated electromyographic activity was linear and highly significant (r = .95 and r = .93). Implications of a neural interpretation of the in vivo torqu-velocity relationship in muscle are discussed.

Electromyography↗

Mutagenicity of fluorene derivatives: a proposed mechanism.

Several derivatives of fluorene, a tricyclic, organic molecule, have been found to induce both frameshift mutations and base-pair substitutions in Salmonella typhimurium strains developed by Ames. Comparisons of the mutagenic potency of these derivatives for several strains of Salmonella suggest the importance of a carbonyl group substituted at the carbon-9 position of mutagenic derivatives, with respect to mutagenic potency. In this study, we present a feasible mechanism for the interaction of mutagenic fluorene derivatives with deoxyribonucleic acid. This mechanism requires the interaction of the mutagenic molecule with carbon-8 of guanine and a second concurrent interaction with the C-4 amino group of an adjacent cytosine residue.

DNA, Bacterial↗

Testing the environment for dispersed mutagens: use of plant bioconcentrators coupled with microbial mutagen assays.

Mutagens dispersed in ecosystems are usually in low concentration and episodic in occurrence. The possibility of detecting such dispersed mutagens by utilizing indigenous bioconcentrator organisms coupled with a microbial mutagen assay offer a useful screening protocol. There are numerous examples of plant and animal species which concentrate toxic substances from the environment. Body extracts of these bioconcentrators can be suitably fractioned and tested for mutagens with various microbial mutagen assays. The fractions may be tested with a broad range of microbial assays covering numerous genetic end points as well as both with and without mammalian microsomal activation. This kind of environmental screening has an advantage over physicochemical techniques, in that sampling techniques are simpler and a wider chemical spectrum can be screened. There are problems inherent with testing a complex biological extract, however. If a reversion assay is used, the metabolite necessary for growth may be present. Toxins may be introduced, either concentrated from the environment in the same way as the mutagen, or produced by the concentrator itself. Finally, the concentrator may also produce an endogenous mutagen which will give spuriously active extracts. Methods for minimizing some of these difficulties are discussed.

Bacteria↗