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Biomedical subjects

W R Bruce

Publications and source records attributed to W R Bruce.

At least 73 records · Page 4Linked to original sources
PubMed1986

Comparison of the fecal microflora in rural Japanese and urban Canadians.

The fecal microflora of nine rural healthy Japanese and eight urban healthy Canadians was examined. The two populations ate typical Japanese and western diets, respectively. The numbers of eubacteria (P less than 0.01), bifidobacteria (P less than 0.05), bacilli (P less than 0.01), lactobacilli and veillonellae and the frequency of occurrence of bifidobacteria were higher in the Japanese than in the Canadians. Higher numbers of bacteroides and lecithinase-negative clostridia were found in the Canadians. Twenty-three genera and over 75 species or biovars were isolated from the feces of Japanese and 18 genera and over 66 species or biovars from the Canadians. The numbers of Bacteroides vulgatus (P less than 0.05), Clostridium coccides (P less than 0.001), and C. tertium (P less than 0.05) and the incidence of B. uniformis (P less than 0.01), C. innocuum (P less than 0.05), and Bacillus spp. (P less than 0.01) were significantly lower in the Japanese than in the Canadians. In contrast, the numbers of Eubacterium aerofaciens (P less than 0.001), and the incidence of Bifidobacterium adolescentis biovar b (P less than 0.01) and Bacillus subtilis (P less than 0.01) were significantly higher in the Japanese than in the Canadians. These findings suggest that significant reductions in anaerobic gram-positive bacilli and increased numbers of bacteroides and clostridia in the feces were induced by the intake of a western diet.

Canada↗
PubMed1986

Effects of calcium and pH on the mucosal damage produced by deoxycholic acid in the rat colon.

A single pass perfusion system was used in anaesthetised, restrained rats to examine the effect of changing the composition of the perfusion fluid on the damage caused to the colonic epithelium by deoxycholic acid. Damage to the colonic surface was monitored with light microscopy, transmission and scanning electron microscopy and with measurements of deoxyribonucleic acid and carbohydrate in the perfusate. New scoring techniques for monitoring alterations in surface epithelium of light microscopy sections were used. The damaging effect of 5 mM deoxycholic acid to the colonic epithelium is inhibited by lowering the pH of the perfusion fluid from 7.9 to 5.5, or by increasing the calcium concentration from 0 to 4 mM. This inhibition is shown to be because of a decreased amount of bile acid in solution. Thus it is not the total concentration of deoxycholic acid in the colon that is responsible for the colonic damage, but the concentration in solution. Although extrapolation to the human situation must be made with caution, the concentration of bile acid in solution in the faecal water may be more relevant to colonic mucosal damage than total bile acid concentration.

Animals↗
PubMed1986

Increase by deoxycholic acid of the colonic nuclear damage induced by known carcinogens in C57BL/6J mice.

Intrarectal exposure of the colon epithelium of the C57BL/6J female mouse to deoxycholic acid [(DCA) CAS: 83-44-3] markedly increased its sensitivity to orally administered 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8]. While 4 mg DMH/kg body weight by itself increased the level of nuclear damage from a background level of 0.2-0.45 aberration per crypt, DMH when combined with DCA at a dose of 150 mg/kg increased the aberrations from 0.2 to 1.75 per crypt. This effect was observed over a wide range of DCA doses (20-300 mg/kg) and was evident when DMH was given up to 10 hours after the DCA. Similar results were observed with DCA in conjunction with benzo[a]pyrene (CAS: 50-32-8) and 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (CAS: 77094-11-2), though in these cases the time at which the peak of nuclear aberrations occurred was somewhat later. No enhancement was seen with DCA and gamma-radiation. These results show that DCA can enhance the nucleotoxic effects of several carcinogens and suggest that DCA can act as a cocarcinogen. The enhancement may be due to the effect of the bile acid on proliferation of the colon epithelial cells or to its effect on the permeability of mucosal cells.

1,2-Dimethylhydrazine↗
PubMed1985

Dietary fiber and cancer: a supplement for intervention studies.

Dietary fiber is one of several variables being considered in the study of the relationship between diet and cancer. Intervention trials in which dietary fiber is increased are the most direct way of assessing the possible role of fiber in this disease. Two dietary snack products have been developed for use in a fiber intervention study: the high-fiber snack (HFS), which supplies 23 g of dietary fiber per day (mostly from wheat bran) and the low-fiber product (LFS), which provides 3.5 g. Over a 12-week period, 28 volunteers consumed the HFS for 6 weeks and the LFS for 6 weeks. Compliance, as assessed by reports, through recovery of a riboflavin marker in the urine and fecal fiber analysis, was good. The only adverse effects reported were mild abdominal discomfort and gas. Serum ferritin and calcium decreased in some subjects, indicating a need to supplement the products with these essential minerals. Consumption of the snacks did not affect total energy intake or the intake of the nutrients monitored.

Adult↗
PubMed1985

Toxicity of orally administered fat to the colonic epithelium of mice.

C57BL/6J mice were given a gavage of from 0.1 to 0.4 ml beef tallow (BT) or corn oil (CO). The damaging effect of the orally administered fat boluses could be visualized 2-4 h later by instilling the excised animal colons with Trypan blue, a vital dye that stains non-viable cells. Microscopic examination of sections prepared at these times revealed that the tall columnar cells on the surface of the normal epithelium were replaced with cells demonstrating flattened, pleomorphic, pyknotic and fragmented nuclei. This phenomenon was quantitated by scoring 100 intercrypt epithelial zones between well-defined crypts. The maximum damage, affecting 25-45% of the epithelial zones, was seen at 2-4 h after treatment with 0.4 ml of BT or CO and the epithelium appeared normal with less than 10% damage at 12 h. The mitotic activity in the colonic crypts was unchanged up to 8 h and then showed a marked increase of 2- to 3-fold at 12-16 h. The severity of the epithelial damage and ensuing mitogenic response was related to the size of the fat bolus. These observations would suggest that the effects of any carcinogens present in the diet or formed in the feces could be enhanced if a fatty meal results in colonic damage and subsequent cell proliferation as we have observed in mice.

Animals↗
PubMed1985

The effect of calcium on the pathogenicity of high fat diets to the colon.

The pathogenicity of lipid components and dietary fats on the colonic epithelium have been studied with five model systems in experimental animals, with rectal perfusion of bile acids, colonic perfusion of bile acid solutions, dietary supplementation with cholic acid, oral boluses of fat, and diets with various levels of fats. The lipid or fat led to colonic epithelial cell cytotoxicity and/or an increase in cell proliferation which was inhibited by supplementary calcium. These results could mean that calcium may reduce the toxicity of high fat diets to the colon and reduce the colonic cancer risk associated with high fat diets.

Animals↗
PubMed1985

Detection of nuclear anomalies in the colonic epithelium of the mouse.

Colon carcinogens produce a variety of nuclear anomalies including pyknotic, karyorrhectic, and micronucleated cells in the colonic epithelium within a few hr. Two model carcinogens, 1,2-dimethylhydrazine and gamma-rays, have been used to determine appropriate techniques, conditions, and scoring criteria for detecting such nuclear anomalies most efficiently. The results show that a rapid and sensitive assay for nuclear anomalies can be conducted with a variety of preparation techniques. We anticipate that the assay will be useful as a screen for potential colon carcinogens in the diet or elsewhere. The assay as recommended by us requires at least five animals per group and takes about 1 hr to analyze. A single sample at 6 or 24 hr after treatment should detect most carcinogens.

Animals↗
PubMed1985

Approaches to understanding the relationship between diet and colon cancer.

Epidemiological research into the etiology of colon cancer has failed to provide consistent evidence on the role of diet. This may have arisen, in part, from two methodological limitations of the studies: the difficulty of obtaining accurate measurements of diet and the lack of variability in diet among the subjects studied. In case-control studies, diet measurement might be improved if current rather than past diet could be studied and this might be appropriate if studies were based on patients with precursor lesions rather than cancer. Precursor lesions might also serve as endpoints for randomized trials of dietary interventions. In both types of studies, laboratory measurements of specific dietary variables should be used to supplement diet questionnaires. Further, controls should not be selected from patients with diet-related diseases and studies should be conducted in communities with sufficient dietary variability to ensure the presence of an appropriate gradient in risk.

Colonic Neoplasms↗
PubMed1984

Human fecal fractions can produce nuclear damage in the colonic epithelial cells of mice.

Nuclear toxicity of several known carcinogens and fecal fractions obtained from 10 healthy individuals was investigated in the colonic nuclear aberration (NA) assay using an intrarectal administration. Two known colon carcinogens, MNNG and DMAB, and a carcinogen of organs other than the colon, B(a)P, induced NA in a dose-related manner. Chromatographic fractions of feces from 10 donors were tested for their ability to produce NA. The dichloromethane fraction for several was active and yielded a significantly positive response which was dose-related. Our study demonstrated that the feces of some healthy individuals contain compound(s) which damage colonic nuclei in a similar manner to that seen with some known carcinogens.

Adult↗
PubMed1984

On distribution of different fecapentaenes, the fecal mutagens, in the human population.

It has been shown by an HPLC analysis using a quarternary solvent mixture in an isocratic mode that human excretors of these fecal mutagens excrete both fecapentaene -12 and -14 but the ratios vary greatly between individuals. Since these mutagens are produced by the bacterial flora of the colon, this may indicate differences in the flora between these individuals or differences in the availability of different precursor molecules in their colons. Any relationship of these findings to the etiology of colonic cancer is not clear.

Adult↗
PubMed1984

Colon cancer and dietary fat, phosphate, and calcium: a hypothesis.

Increased dietary fat was suggested to promote colon cancer by increasing the levels of free ionized fatty acids and bile acids in the colon contents. In the presence of calcium ions the irritating and toxic effects of the free acids on colon epithelial cells could be reduced by being converted to insoluble calcium soaps. The level of supplementary dietary calcium to supply adequate calcium and thus reduce the potential toxicity of dietary fat was considered.

Bile Acids and Salts↗
PubMed1984

Damaging effect of dietary components to colon epithelial cells in vivo: effect of mutagenic heterocyclic amines.

The nuclear damaging effects of the mutagenic heterocyclic amines 3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole [(Trp-P-1) CAS: 62450-06-0; 1,4-dimethyl-5H-pyrido(4,3-b)indol-3-amine], 3-amino-1-methyl-5H-pyrido(4,3-b)indole [(Trp-P-2) CAS: 62450-07-1; 1-methyl-5H-pyrido(4,3-b)indol-3-amine], 2-amino-6-methyldipyrido(1,2-a:3',2'-d)imidazole [(Glu-P-1) CAS: 67730-11-4; 6-methyldipyrido(1,2-a:3',2'-d)imidazol-2-amine], 2-amino-3-methylimidazo(4,5-f)quinoline [(IQ) CAS: 76180-96-6; 3-methyl-3H-imidazo(4,5-f)quinolin-2-amine], and 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ) on colon epithelial cells of C57BL/6J mice were investigated. The numbers of nuclear aberrations (NA) per crypt was determined 24 hours after oral administration of these amines at various dose levels. Trp-P-1, Trp-P-2, and Glu-P-1 increased the incidence of NA approximately twofold to threefold above the background level (0.15 NA/crypt) even at near-lethal dose levels. However, IQ and MeIQ increased the incidence fivefold to tenfold at nonlethal dose levels ranging from 200 to 800 mg/kg body weight and from 50 to 200 mg/kg body weight, respectively. IQ intubation in the morning (11 a.m.) produced the maximum response in 24 hours, whereas intubation in the evening (7 p.m.) produced maximum response in 12 hours. The colon-specific toxicity of the heterocyclic amines at approximately 35% of their maximum tolerated dose levels was in the order of MeIQ greater than IQ greater than Trp-P-2 greater than Trp-P-1 greater than or equal to Glu-P-1.

Animals↗
PubMed1984

Mixed hyperplastic adenomatous polyps--an underdiagnosed entity. Report of a case of adenocarcinoma arising within a mixed hyperplastic adenomatous polyp.

We report a case of colonic adenocarcinoma arising within a polyp with mixed morphology of a hyperplastic polyp and tubular adenoma. Despite the relatively small size of the polyp, two isolated foci of adenocarcinoma in situ were present and tumor islands invaded the submucosa. Isolated areas, morphologically resembling hyperplastic glands, and varying degrees of atypia. Though rare, some hyperplastic polyps may be precursors of adenomas.

Adenocarcinoma↗
PubMed1983

Radiation induction of mutations affecting sperm morphology in mice.

To investigate the basis of the sperm abnormality assay, studies have been made of the frequency of sperm abnormalities in the genital tracts of the progeny of irradiated males. Male C57BL/6 mice were irradiated (75-600 rad X-rays to the testes) and were then bred in the pre-sterile period to untreated C57BL/6 females. The sperm of their male progeny were examined for the frequency of sperm abnormalities. Variant males with clearly elevated levels of sperm abnormalities were more frequently seen amongst the progeny of irradiated fathers than with the progeny of sham-irradiated controls (10 in 170 compared with 2 in 188; P less than 0.02). Although no clear dose-response relation could be discerned with the number of animals studied, similar differences were observed with irradiated male SWR, C3H/He in inbred crosses and with C57BL/6 in hybrid crosses with C3H/He females. In contrast, matings of males made at longer times following irradiation did not lead to a significant increase in the number of affected progeny for the number tested. Breeding experiments with the affected F1 males showed that the sperm morphology defect could be transmitted in 7 of 19 cases. Parallel cytogenetic studies showed that 3 of the initial affected progeny had detectable reciprocal translocations and that in 2 of these cases the translocation was transmitted with the sperm defect. The studies thus showed that radiation can induce mutations that affect the levels of sperm abnormalities and that these mutations can be associated with reciprocal translocations.

Animals↗
PubMed1983

Comparison of the effects of 1,2-dimethylhydrazine and cyclophosphamide on micronucleus incidence in bone marrow and colon.

An in vivo micronucleus assay has been developed that utilizes colonic epithelial cells. The genotoxic effects of 1,2-dimethylhydrazine (54-07-3), a colon carcinogen, and of the nitrogen mustard, cyclophosphamide (50-18-0), on the bone-marrow polychromatic erythrocytes and on colonic epithelium from mice were compared using micronucleus induction in each organ as the end point. In the bone marrow, cyclophosphamide was a potent inducer of micronuclei, while 1,2-dimethylhydrazine administration had little effect on the micronucleus incidence. In the colon, 1,2-diemthylhydrazine was an effective inducer of micronuclei. Thus, the colonic micronucleus assay appears to be a potentially useful test for the detection of colon carcinogens.

1,2-Dimethylhydrazine↗