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Biomedical subjects

W R Bruce

Publications and source records attributed to W R Bruce.

At least 91 records · Page 5Linked to original sources
PubMed1983

Mutagenicity of different fractions of extracts of human feces.

An extraction-fractionation scheme for the isolation of non-volatile fecal mutagens is described. Extraction of feces was with acetone, and a 2-step fractionation scheme employing silica gel SepPak cartridges and normal-phase high-pressure liquid chromatography was used. Assay of mutagens was with the standard plate mutagenicity assay with Salmonella typhimurium tester strains TA98 and TA100, with and without the Aroclor induced S9 microsomal activation system. Single feces samples from 24 donors from a wide socioeconomic spectrum were tested. It was found that most fecal mutagenicity extracted by aqueous acetone could be attributed to a lipid soluble mutagen active on both TA98 and TA100 that has been previously reported.

Chromatography↗
PubMed1983

Calcium ameliorates the toxic effect of deoxycholic acid on colonic epithelium.

The effect of a deoxycholic acid instillation on colonic epithelium was investigated and compared with the effect of an intervention scheme in which deoxycholic acid (DCA) treated mice received oral supplements of calcium lactate. The morphology of colonic tissue exposed to DCA was markedly affected when compared to that of untreated controls. Inflammation, edema, and necrosis preceded elevated numbers of mitotic figures appearing 24 h to 48 h after DCA treatment. Proliferative activity as measured by tritiated thymidine uptake and autoradiography was increased 2.5-fold in colonic crypts of DCA treated mice. In contrast mice receiving multiple oral supplements of calcium lactate showed minimal tissue necrosis due to DCA administration and the frequency of mitotic events and cellular proliferation activity remained similar to levels seen in untreated controls. Sequestration of bile acids by calcium salts may provide a scheme for inhibiting the untoward effects of bile acids on the colonic epithelium and a mechanism for blocking the reported co-carcinogenic activity of these agents.

Animals↗
PubMed1983

Early histopathologic events to evolution of colon cancer in C57BL/6 and CF1 mice treated with 1,2-dimethylhydrazine.

After administration of the intestinal carcinogen 1,2-dimethylhydrazine (DMH), C57BL/6J and CF1 mice were observed for early precursor lesions to large bowel cancer. Among the initial events seen following DMH treatment, an abrupt reduction in colonic DNA synthesis was the earliest lesion detectable. The frequency of aberrant colonic nuclei rose shortly after DMH treatment, reaching a maximum value 24 hours later and remaining elevated for 3 days following the exposure. Mucin changes, detected histochemically, and cell kinetic alterations in crypt proliferation rates were observed much later and were a constant feature for both strains following 4 weekly treatments with DMH, while carcinomas appeared in all animals 32 weeks after the start of DMH treatment. The quantitative comparison of these histopathologic observations for the early detection of colon cancer suggests that the induction of colonic nuclear aberrations in the mucosa of the large bowel might provide a sensitive and rapid indication of genotoxicity to this organ and thus might provide the basis for a screening methodology for colon carcinogens.

1,2-Dimethylhydrazine↗
PubMed1983

Nuclear aberrations as a short-term test for genotoxicity to the colon: evaluation of nineteen agents in mice.

The genotoxicity of 16 agents including several hydrazines, nitrosamines, aromatic amines, polycyclic hydrocarbons, and other related compounds and three known inhibitors of carcinogenesis was assessed in the murine colonic nuclear aberration assay. Of the seven agents considered positive for colonic DNA damage, five were large bowel carcinogens. All structural analogues of the intestinal carcinogens that are tumorigenic for other organs, with the exception of benzo[a]pyrene, were negative in the colonic nuclear aberration assay as were all noncarcinogens tested. The metabolic inhibitor disulfiram completely inhibited 1,2-dimethylhydrazine-induced colonic nuclear damage, while inhibition was less marked for the antioxidants butylated hydroxyanisole and caffeic acid. The versatility of the assay as an indicator of colonic genotoxicity resulting from carcinogen exposure is discussed.

1,2-Dimethylhydrazine↗
PubMed1983

Colonic mucus in human fetal development.

The labelling behaviour of specimens of human fetal colon at different stages of development was examined using eight fluorescently labelled lectins with preferences for different carbohydrate structures. Peanut agglutinin (PNA) binding can be demonstrated in specimens from fetal colons between the 4th and 5th week and the 5th and 6th lunar month. Since CEA may bind to similar structures as PNA, an answer was sought to the question whether these structures are in fact identical. While there is evidence in favour of non-identity, it is not entirely conclusive. PNA-binding to fetal tissues is of interest since PNA binds to adult transformed colonic tissues, but not to normal ones.

Antigens, Neoplasm↗
PubMed1982

An analytical method for simple N-nitrosamides.

A clean-up method is described which sufficiently removes interfering chemicals from feces so that the colorimetric procedure of Preussmann & Schaper-Druckrey (1972), or HPLC with UV detection, can be used reliably to detect N-nitrosamides. The method has given reasonably good recoveries of four different N-nitrosamides intentionally added to feces. The method, or parts of it, should be applicable to the clean-up of other complex samples, such as food, biological tissues and body fluids.

Colorimetry↗
PubMed1982

Analysis and formation of nitrosamines in the human intestine.

The method employed for nitrosamine analysis gave high recovery values and did not produce artefactual nitrosamines. Nitrosation reactions are not catalysed by the microbial ecosystem of human feces. Rapid loss of nitrate and nitrite in feces also precludes nitrosamine formation, unless very high concentrations of precursors are present. These concentrations are not physiological and it is therefore unlikely that N-nitroso compounds form in the lower gastrointestinal tract of man.

Feces↗
PubMed1981

Strategies for dietary intervention studies in colon cancer.

As a result of many studies in descriptive and analytic epidemiology, in animal carcinogenesis, and in the direct examination of body fluids for mutagens/carcinogens, it is possible to develop a list of dietary factors that may be associated with the high rate of colon cancer and related cancers in Western countries. This paper is concerned with the design of intervention studies to clarify which of these factors is important. The size of such intervention trials is influenced primarily by two factors: the incidence of the disease outcome studied in a control population and the magnitude of risk reduction in a treated group. Calculations based on a variety of assumptions suggest that a randomized trial in which cancer mortality is measured as the outcome of the intervention in a healthy population is probably too costly to be justified by current evidence linking the disease to diet. However, precursor lesions can be considered as an alternative outcome. The choice of the precursor lesion depends on the link to the disease in question, the prevalence of the lesion in the population, and the ease of detection. Recent developments in the application of endoscopic methods and in the description of the pathologic process leading to cancer suggest the use of gastrointestinal polyps as "precursor lesions" as the outcome of a trial. We illustrate these points with a protocol for a study in progress, a randomized double-blind study of the effect of ascorbic acid and alpha-Tocopherol on the rate of recurrence of colorectal polyps.

Adult↗
PubMed1981

Reevaluation of nitrate and nitrite levels in the human intestine.

Analyses of human fecal and ileostomy samples by a method that is insensitive and free from interferences indicate that nitrate and nitrite levels in the intestine are lower than reported previously. Fecal nitrate and nitrite concentrations ranged from 0 to 14 mumol/kg (0 to 0.9 ppm) and 5 to 19 mumol/kg (0.3 to 0.9 ppm), respectively. Ileostomy samples contained from 0 to 7 mumol/kg (0 to 0.4 ppm) and 0 to 15 mumol/kg (0 to 0.7 ppm) for nitrate and nitrite, respectively. We also showed that, when deliberately added to feces samples, nitrate and nitrite were destroyed during a two-hr incubation period in a reaction that depended on the presence of microorganisms. The results suggest that conditions in the lower gastrointestinal tract favor denitrification, not nitrification as had been proposed previously.

Adolescent↗
PubMed1981

Absence of volatile nitrosamines in human feces.

Using a method for nitrosamine analysis that gives high recovery values and that is free from artifactual synthesis of nitrosamines, we have shown that human feces do not contain volatile nitrosamines (detection limit, 0.1 to 0.5 microgram/kg). We also showed that nitrosation reactions are not catalyzed by fecal organisms. Following a 2-day anaerobic incubation of feces with either a secondary amine (dimethylamine, dipropylamine, or morpholine) or nitrite, no nitrosamine was formed. When the amine and nitrite were added together, nitrosamine was formed, but at a level of 2 to 20% of that formed in autoclaved feces under the same conditions. Nitrosamines were stable following anaerobic incubation with feces for up to 4 days. These results suggest that fecal organisms inhibit the chemical formation of nitrosamines instead of catalyzing it. When morphine and nitrate were added together, nitrosomorpholine was formed. Morpholine nitrosates so rapidly that it intercepts nitrite formed by the action of nitrate reductase before the nitrite can be further reduced. However, very high concentrations of morphine and nitrate, which are far from the conditions in normal feces, were required to form measurable nitrosomorpholine. We may conclude that N-nitroso compounds are unlikely to be formed in any significant amounts in the human colon.

Feces↗
PubMed1979

Sperm size abnormalities in homozygous and heterozygous In(5)9Rk mice.

Sperm abnormalities were scored in In(5)9Rk homozygotes, heterozygotes and in the inbred strains, C57BL/6J, C3H/HeJ, DBA/2J and JUFaCt, used to produce the geterozygotes. The sperm abnormalities of the inversion heterozygotes were remarkable, about 40% were either double-headed or abnormally large in size. The double-headed sperm had head dimensions similar to those of normal-sized sperm, but the large sperm heads were 1.2 times longer and 1.3 times wider and presumably had twice the usual nuclear volume. This observation suggests that the anaphase bridge formed in inversion heterozygotes resulting from the paracentric inversion may constitute an impediment to cytokinesis and may lead to two genomes being packaged into a single sperm. If this is a general phenomenon, sperm morphology may provide a useful screen for paracentric inversions.

Animals↗
PubMed1979

The mutagenic activity of 61 agents as determined by the micronucleus, Salmonella, and sperm abnormality assays.

A comparison of two rapid and inexpensive in vivo mammalian assays and the Ames Salmonella assay is presented for 61 agents; Acetylsalicylic acid; Acriflavine; Actinomycin D; 2(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2); Aflatoxin B1; 2-aminofluorene; Aminopterin; Aroclor 1254; Ascorbic acid; Azathioprine; Benzo(a)pyrene; 5-Bromo-2'-deoxyuridine; Busulphan, Butylated hydroxytoluene; Cadmium chloride; Caffeine; Calcium cyclamate; Chloral hydrate; Chloromycetin succinate; Codeine phosphate, Colchicine; Cycloheximide; Cyclophosphamide; DDT; 2,4-Diaminoanisole; Dibutylnitrosamine; 9, 10 Dimethyl-1,2-benzanthracene; 1,1-Dimethylhydrazine; Dimethylnitrosamine; Epinephrine; Ethyl methane sulphonate (EMS); 2-formylamino-4-(5-nitro-2-furyl)thiazole (FANFT); 2-(2-formylhydrazino)-4-(5-nitro-2-furyl)thiazole (FNT); Glucose, Griseofulvin; Hycanthone methane sulphonate; Hydroxyurea; 5-Iodo-2'-deoxyuridine; Lead acetate; Mechlorethamine; 3-Methylcholanthrene; Methyl mercury acetate; Methyl methane sulfonate (MMS); N-methyl-N-nitro-N'-nitrosoguanidine; Mitomycin C; Monosodium glutamate; 1-Naphthalamine; 2-Naphthalamine; Nitrofurazone; 4-Nitro-O-phenylene diamine; 4-Nitro-quinoline-1-oxide (4-NQO); Phenobarbitone; Procarbazine; Quinacrine dihydrochloride; Radiation (gamma-rays); Sodium chloride; Triethylene thiophosphoramide; Trimethyl phosphate; Tris(2-methyl-1-arizidinyl) phosphine oxide; Urethan; Vinblastine. The results support the concept of multiple assays for mutagenicity and show that some combinations of assays are superior to others.

Animals↗
PubMed1979

Effects of cannabinoids on sperm morphology.

Sperm morphology was studied in hybrid mice of genotype (C57BL X C3H)F1 following treatment with specific cannabinoids. Mice were treated for 5 consecutive days with the specific cannabinoid; 35 days after the last treatment, epididymal sperm were scored in the light microscope and assessed in the scanning electron microscope. The animals treated with delta9-tetrahydrocannabinol (delta9-THC) and cannabinol (CBN) had a statistically higher incidence of abnormal sperm than the controls. The incidence of abnormal sperm in the animals treated with cannabidiol (CBD) was not statistically different from the control value. The relative toxicity of the cannabinoids in these studies was delta9-THC greater than CBN greater than CBD. Normal sperm have a smooth kidney-shaped head with a prominent hook; abnormal sperm have shapes which include heads without hooks, banana-shaped heads, amorphous heads and folded heads.

Animals↗
PubMed1979

Volatile N-nitrosamines in the urine of normal donors and of bladder cancer patients.

Volatile N-nitrosamines were detected in the urine of male volunteers with gas-liquid and high-pressure liquid chromatography interfaced to the thermal energy analyzer. Of 50 samples from normal males, 10 contained nitrosodimethylamine (0.02 to 0.10 micrograms/liter), 6 contained nitrosodiethylamine (0.02 to 3.10), 9 contained nitrosomorpholine (0.006 to 0.67), and none contained nitrosodibutylamine. Of 4 samples from bladder cancer patients, 2 contained nitrosodibutylamine (0.35 and 0.66). Cigarette smoking did not appear to be related to the pattern or amount of urinary volatile N-nitrosamines. The possibility that the N-nitrosamines arise from the diet or from endogenous production is considered.

Adult↗