Biomedical subjects

J A Milner

Publications and source records attributed to J A Milner.

At least 55 records · Page 3Linked to original sources

PubMed1996

Diallyl disulfide suppresses the growth of human colon tumor cell xenografts in athymic nude mice.

The present studies examined the anti-proliferative effects of diallyl disulfide (DADS) on the growth of human colon tumor cell line, HCT-15, xenografts in 6-wk-old female NCr nu/nu mice with an initial body weight of 20-22 g. Intraperitoneal injection of 1 mg DADS thrice weekly reduced tumor volume by 69% (P < 0.05) without apparent ill consequences such as altered growth of the host. Providing this quantity of DADS intragastrically also inhibited growth of the HCT-15 tumor. At equivalent DADS dosages, intraperitoneal treatment was proportionately more effective (P < 0.05) in reducing tumor growth than gastric intubation. Tumor inhibition caused by DADS (0.5 mg thrice weekly) was similar to that occurring with 5-fluorouracil (5-FU) treatment (0.5 mg thrice weekly). Combining DADS and 5-FU was no more effective in inhibiting tumor growth than using either compound alone. However, concurrent DADS treatment significantly (P < 0.05) inhibited the depression in leukocyte counts and spleen weight and prevented the elevated plasma urea caused by 5-FU treatment. These data suggest that DADS, a constituent of garlic oil, reduces the toxicity of 5-FU and is an effective antitumorigenic agent against xenografts resulting from an established human colon tumor cell line.

Administration, Oral↗

PubMed1996

Dietary rosemary suppresses 7,12-dimethylbenz(a)anthracene binding to rat mammary cell DNA.

Commercially available ground rosemary powder was examined for its ability to modify the in vivo binding of 7,12-dimethylbenz(a)anthracene (DMBA) metabolites to mammary cell DNA in 55-d-old rats fed diets containing varying quantities and types of lipids. Supplementing a casein-based diet containing 20% corn oil with 1 % rosemary for 2 wk reduced by 76% the occurrence of DMBA-induced DNA adducts occurring 24 h after treatment with 50 mg DMBA/kg body weight. A comparable reduction in DNA adducts (66%) occurred when 0.5% rosemary was added to a diet containing 20% corn oil, and the quantity of DMBA given was reduced to 25 mg/kg body weight. The reduction in the occurrence of adducts occurring 24 h after DMBA treatment caused by 0.5% dietary rosemary was greater (P < 0.05) when added to a diet containing 20% corn oil than when added to a diet containing 5% corn oil and 15% coconut oil. Rosemary, 1% but not 0.5%, reduced DMBA-induced DNA adducts when the diet contained 5% corn oil. These studies demonstrate that rosemary is effective in reducing the binding of DMBA metabolites to rat mammary cell DNA. Furthermore, the present studies demonstrate that the benefits of rosemary are dependent on the source and concentration of dietary lipids.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1996

Garlic: its anticarcinogenic and antitumorigenic properties.

Overall, several investigations indicate that garlic and its organic allyl sulfur components inhibit the cancer process. Furthermore, these studies reveal that the benefits of garlic are not limited to a specific species, a particular tissue, or a specific carcinogen. Finally, odor is not a prerequisite for the protection provided by garlic against the initiation of chemical carcinogenesis. Although the water-soluble compound S-allyl cysteine is effective in reducing the risk of chemically induced tumors in experimental animals, it has no effect on established tumors. However, oil-soluble compounds such as diallyl disulfide are effective in reducing the proliferation of neoplasms. Although the evidence supports the benefits of garlic, additional evidence is needed to determine the quantity needed by humans to minimize cancer risk.

Anticarcinogenic Agents↗

PubMed1995

Serum selenium and colonic neoplastic risk.

BACKGROUND: Selenium deficiency has been associated with cancer risk in several organs. This association was investigated in neoplasia of the colorectum. DESIGN: A case-control study is reported with two patient series, colorectal cancer and colorectal adenomatous polyps, and a control group found to be free of colorectal neoplasia. Diagnosis was determined by colonoscopy and histologic review of suspected neoplasms. Serum drawn at the time of colonoscopy was subsequently assayed for selenium content, and quartiles based on selenium were defined. Crude and adjusted odds ratios with 95 percent confidence intervals for adenoma related to selenium were calculated, controlling for known or suspected risk factors including gender, age, race, body mass index, family history, tobacco use, alcohol consumption, serum beta carotene, serum alpha tocopherol, and serum ferritin. RESULTS: There were 138 controls who had no neoplastic disease, 139 adenoma patients, and 25 cancer patients. For adenoma, comparing higher quartiles of selenium to the first (lowest selenium), the adjusted odds ratio for the second quartile was 1.7 (95 percent confidence interval, 0.8-3.7), the third quartile was 1.4 (0.7-3.2), and the fourth (highest selenium) quartile was 1.8 (0.9-4). The odds ratios for cancer patients were 0.8 for the second quartile, 1 for the third quartile, and 1.7 for the fourth quartile. CONCLUSION: No trend could be detected toward a protective effect of higher levels of serum selenium for colonic benign or malignant tumors.

Adenoma↗

PubMed1995

Use of commercial enzyme kits and fatty acid production for the identification of Serpulina hyodysenteriae: a potential misdiagnosis.

The accuracy of identification of Serpulina hyodysenteriae strains grown in a complex medium was 90% when 2 commercial test kits were used. Unlike the other S. hyodysenteriae strains, S. hyodysenteriae strain P35/2 was unusual in being indole negative. The nonpathogenic intestinal spirochete PWS/A, which is from a different species, was indole positive and alpha-galactosidase negative. Identification of these spirochetes on the basis of these kits alone would have been incorrect. The analysis of volatile fatty acids by gas chromatography showed that the ratio of acetic to butyric acid was from 11:1 to 44:1 for S. hyodysenteriae strains, which distinguished them from the other spirochetes. The exception was PWS/A (acetic: butyric of 32:1), but this spirochete, unlike the S. hyodysenteriae spirochetes, also produced isobutyric acid. Short chain fatty acid (SCFA) analysis by high-performance liquid chromatography detected different SCFAs in addition to acetic and butyric acids. These additional SCFAs did not contribute to further differentiation of the porcine spirochetes.

Animals↗

PubMed1994

Dietary garlic suppresses DNA adducts caused by N-nitroso compounds.

The present studies examined the impact of a processed garlic powder on the in vivo occurrence of DNA adducts caused by N-nitroso compounds (NOC) in rats. Addition of 2% garlic powder to diets containing aminopyrine and sodium nitrite (each at 600 mg/kg) reduced the occurrence of both 7-N-methyldeoxyguanosine (7-N-mG) and 6-O-methyldeoxyguanosine (6-O-mG) adducts to rat liver DNA by approximately 55%; and over 80% when 4% garlic was provided. Dietary supplementation with garlic powder (2 and 4%) also reduced the occurrence of 7-N-mG and 6-O-mG adducts by approximately 40 and 60% respectively, in rats intubated with N-nitrosodimethylamine (150 mg/kg body wt). The quantity of 7-N-mG and 6-O-mG adducts in mammary tissue of rats given intravenous N-methyl-N-nitrosourea (50 mg/kg body wt) was reduced over 50% in rats fed 2% garlic compared to controls. The depression in the occurrence of these adducts was approximately 70% when dietary garlic was increased to 4%. These experiments suggest the reduction in DNA adducts caused by processed garlic powder likely reflects a depression in the formation of NOC from precursors and changes in the bioactivation and/or denitrosation of NOC.

Animals↗

PubMed1994

Dietary selenite modifies glutathione metabolism and 7,12-dimethylbenz(a)anthracene conjugation in rats.

The present studies determined the impact of dietary selenite on glutathione homeostasis in liver and mammary tissue and its relationship to biliary excretion of 7,12-dimethylbenz(a)anthracene (DMBA) conjugates. In Experiment 1, liver and mammary tissue concentration of reduced glutathione (GSH) and activities of gamma-glutamylcysteine synthetase (GCS), glutathione reductase (GR) and glutathione S-transferases (GST) were positively correlated with tissue selenium concentration in female rats fed semipurified diets supplemented with sodium selenite (0.05 to 4 mg Se/kg). The magnitude of the response was dependent upon total selenite intake and the tissue examined. Glutathione peroxidase activity did not correlate with tissue GSH concentration. Because both selenite and BHT have been reported to elevate liver GSH, Experiment 2 compared these agents (4 mg Se/kg and 6 g/kg BHT/kg, respectively) on the biliary excretion of DMBA metabolites. Five major biliary DMBA conjugates, three GSH and two beta-glucuronide, were identified. Dietary addition of selenite or BHT enhanced the excretion of these DMBA conjugates by over 100% during the 15-h collection period. These investigations suggest that dietary selenium can alter the concentration of GSH and the activities of three glutathione-dependent enzymes in mammary and liver, accounting for part of the expanded biliary excretion of DMBA conjugates. Enhanced biliary loss of DMBA conjugates likely relates to the reported depression in DMBA binding to mammary cell DNA and the inhibition of DMBA carcinogenesis caused by dietary selenite.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1994

Chemotactic response to mucin by Serpulina hyodysenteriae and other porcine spirochetes: potential role in intestinal colonization.

Chemotaxis of porcine spirochetes towards a variety of mucins was measured quantitatively by a capillary method. A chemotaxis buffer consisting of 0.01 M potassium phosphate buffer (pH 7.0) and 0.2 mM L-cysteine hydrochloride was necessary for chemotaxis of spirochetes. The optimum incubation time and incubation temperature were 1 h and 40 degrees C, respectively. The mucin concentration also affected the chemotaxis observed, and a concentration of 1% (wt/vol) was near the optimum. Virulent Serpulina hyodysenteriae strains were chemotactic towards 1% (wt/vol) hog gastric mucin and 1% (wt/vol) porcine colonic mucin but not towards 1% (wt/vol) bovine submaxillary mucin. Virulent S. hyodysenteriae strains were significantly more chemotactic than avirulent strains of S. hyodysenteriae (SA3 and VS1), Serpulina intermedius, and Serpulina innocens. Other spirochetes belonging to the proposed group of spirochetes Anguillina coli were also not chemotactic. Pathogenicity of S. hyodysenteriae strains that cause swine dysentery may, in part, be attributed to their attraction to porcine intestinal mucus.

Animals↗

PubMed1993

Impact of organosulfur compounds in garlic on canine mammary tumor cells in culture.

Six organosulfur compounds found in garlic were examined for their ability to alter the growth of canine mammary tumor cells (CMT-13) in culture. Water-soluble organosulfur compounds (S-allyl-cysteine, S-ethyl-cysteine and S-propyl-cysteine) did not significantly alter the growth of CMT-13 cells when added to cultures at 1.0 mM or less. However, oil-soluble organosulfur compounds (diallyl sulfide, diallyl disulfide and diallyl trisulfide) markedly inhibited growth. Increasing addition of diallyl disulfide (DADS) resulted in a progressive decrease in CMT-13 cell growth. Addition of glutathione before DADS markedly decreased the severity of the growth inhibition. Treatment with DL-buthionine-SR-sulfoxamine, a specific inhibitor of glutathione synthesis, accentuated the growth inhibition caused by DADS. These studies show that some organosulfur compounds found in garlic are effective inhibitors of the growth of the neoplastic CMT-13 cell. The inhibitory effects of these compounds are modified by intracellular glutathione.

Allyl Compounds↗

PubMed1993

Differential effects of cyanohydroxybutene and selenium on normal and neoplastic canine mammary cells in vitro.

The in vitro responses of canine mammary tumor (CMT-13) cells and normal canine mammary (NCM) cells to 1-cyano-2-hydroxy-3-butene (CHB), a naturally occurring nitrile in cruciferous plants, and selenium (Se) were investigated. CHB at 10 and 20 mM inhibited growth and viability of CMT-13 and NCM cells, respectively. This differential sensitivity was associated with a decreased ability of CMT-13 cells to increase intracellular glutathione (GSH) in comparison to NCM cells. Exposure of both cell types to 3.2 microM Se as sodium selenite alone had no effects, but addition of 3.2 microM Se 24 h after exposure to non-toxic doses of CHB resulted in a substantial decrease in growth of CMT cells, while NCM cells remained unaffected. The synergy noted between CHB and Se in inhibiting growth and viability of neoplastic mammary cells at levels not toxic to normal mammary cells is promising initial evidence that CHB could have a role in chemoprotection or chemotherapy.

Alkenes↗

PubMed1993

Selenium status of infants is influenced by supplementation of formula or maternal diets.

Plasma selenium of infants fed proprietary formula was significantly less than that in infants fed human milk. Addition of selenite to the formula (0.253 mumol Se/L) increased plasma selenium and activities of glutathione peroxidase (GPx) and total peroxidase (Px). However, erythrocyte selenium decreased significantly during the 12-wk study in infants receiving human milk or formula with or without supplemental selenite. Infants fed human milk from women receiving 0 or 200 micrograms supplemental selenium as selenomethionine or selenium-enriched yeast had plasma selenium that paralleled changes in their selenium intake. Plasma GPx and Px activities were unrelated to human milk selenium intake. Milk from women given either selenium supplement prevented the decline in infant erythrocyte selenium. Results of these studies suggest that the method of feeding modifies the infant's apparent selenium status and that the molecular form of selenium provided and/or its interaction with other milk constituents are determinants of infant selenium status.

Anthropometry↗

PubMed1993

Selenium status of lactating women is affected by the form of selenium consumed.

The impact of providing selenomethionine (2.7 mumol Se) or selenium-enriched yeast (2.9 mumol Se) on the selenium status of lactating and nonlactating women with customary intakes of approximately 1.3 mumol Se/d was studied. Plasma selenium declined in unsupplemented lactating women but not in nonlactating women. Selenomethionine increased plasma selenium in both lactating and nonlactating women whereas selenium-enriched yeast increased plasma selenium only in nonlactating women. Erythrocyte selenium concentration was not significantly modified by lactation. Plasma glutathione peroxidase (GPx) activity decreased with duration of lactation in unsupplemented women and selenomethionine or selenium-enriched yeast supplementation prevented the decline. Milk selenium declined markedly for 20 wk after parturition in unsupplemented women. Selenomethionine significantly increased milk selenium concentrations whereas selenium-enriched yeast prevented a decline. These results clearly show that the source of selenium provided to lactating women can significantly influence selected indexes of selenium status, including milk selenium concentration.

Adolescent↗

PubMed1993

Impact of various sources of garlic and their constituents on 7,12-dimethylbenz[a]anthracene binding to mammary cell DNA.

The present studies assessed the impact of various sources of garlic and their constituents (water- and ethanol-extracts and S-allylcysteine) on the in vivo binding of the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) to rat mammary cell DNA. The provision of dietary raw garlic powder (2%) or its water-extract (1.5%) reduced DMBA-DNA binding by 33 and 46% respectively. Dietary supplementation with a commercially available deodorized garlic powder (powder A) at 2 or 4% depressed the occurrence of adducts by 50 and 78% respectively, while providing a commercially available high sulfur garlic preparation (powder B) at 2% reduced binding by 56%. A pair-feeding study revealed that the depression in carcinogen binding was independent of food intake or weight gain. Although 1% raw garlic powder did not significantly influence the occurrence of DMBA-DNA adducts, an equivalent as the water-extract (0.75%), the ethanol-extract (0.015%) or commercially available powders (A and B) reduced DMBA adducts in mammary tissue by 44, 25, 71 and 65% respectively. Dietary fortification with S-allylcysteine (SAC), a water-soluble constituent of processed garlic, caused a progressive decrease in the binding of DMBA to DNA. Studies with SAC suggest the primary effect of garlic and its constituents is on the bioactivation and binding of the carcinogen rather than DNA repair. These data reveal that several forms of garlic are effective, although variable, in altering carcinogen bioactivation and presumably chemically induced carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1992

Influence of intracellular glutathione on selenite-mediated growth inhibition of canine mammary tumor cells.

The present studies demonstrate that the ability of supplemental selenite to alter the in vitro growth of canine mammary tumor cell line 13 was dependent on the quantity and duration of selenium exposure and on the culture density. Exposure to 3.2 microM selenite did not significantly alter growth but led to an increase in intracellular glutathione (GSH). The severity of growth inhibition between 3.2 and 9.6 microM selenite was dependent on the duration of exposure and culture density. The toxicity of selenite generally increased as the culture density increased. Likewise, changes in intracellular GSH were dependent on the quantity and duration of selenite exposure and the culture density. Depressing intracellular GSH by increasing the culture density or by incubating with buthionine sulfoximine; a specific inhibitor of gamma-glutamyl cysteine synthetase, increased the severity of growth inhibition caused by selenite and markedly increased cellular retention of selenium. Nevertheless, marked cellular retention of selenium did not occur until growth was inhibited by more than 50%. The present studies revealed that the log of the molar ratio of GSH to selenium correlated negatively with the severity of growth inhibition (P less than 0.0001). These studies suggest that cellular toxicity of selenite is dependent on the regulation of the GSH:selenium ratio. An inability to regulate this ratio likely leads to the accumulation of toxic seleno compounds.

Animals↗

PubMed1992

Inhibition of 7,12-dimethylbenz[a]anthracene-induced mammary tumors and DNA adducts by garlic powder.

The present studies determined the influence of dietary supplements of garlic powder (0, 1, 2 or 4%) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors and on the in vivo occurrence of mammary DMBA-DNA adducts in rats. Diets were offered 2 weeks before and 2 weeks following DMBA treatment (25 mg/kg body wt). An additional group was fed the 2% garlic powder diet throughout the 20 week study. Although food intake and weight gain were not influenced, dietary garlic powder supplementation did significantly delay the onset of first tumors (P < 0.01) and did reduce the final mammary tumor incidence (P < 0.01). Consumption of garlic powder also significantly depressed the in vivo binding of DMBA to mammary cell DNA. Binding of both anti- and syn-dihydrodiol epoxides to DNA was depressed in rats fed supplemental garlic powder. The activity of glutathione S-transferase (GST) in mammary and liver tissue from rats fed 2% dietary garlic powder was higher than observed in tissues from rats fed the basal diet. No further increase in GST activity occurred when the dietary garlic content was increased from 2 to 4%. Final mammary tumor incidence was found to correlate positively with total DMBA-DNA binding and the quantities of individual DMBA-DNA adducts. The present studies demonstrate that garlic powder is effective in inhibiting DMBA-induced mammary tumors, possibly by reducing DMBA-DNA binding.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1992

Age, dietary selenium and quantity of 7,12-dimethylbenz(a)anthracene influence the in vivo occurrence of rat mammary DNA adducts.

The present studies determined the impact of age, dietary selenium and 7,12-dimethylbenz(a)anthracene (DMBA) dosage on the occurrence of DMBA-DNA adducts in rat mammary tissue. Diets formulated to contain selenium, as sodium selenite, at 0.1 (control) or 2.0 mg/kg were fed for 2 wk before DMBA treatment. Food intake and weight gain were not influenced by selenium intake. Anti- and syn-dihydrodiol epoxide adducts reached maximum binding by 24 and 36 h, respectively, after treatment with DMBA. Consumption of the diet containing 2.0 mg Se/kg inhibited the appearance of both anti- and syn-adducts by approximately 50% compared with controls. The occurrence of DMBA-DNA adducts correlated with a dosage of DMBA from 5 to 50 mg/kg body wt (r greater than or equal to 0.95). The ability of supplemental selenite to lower DMBA binding to mammary cell DNA increased as the quantity of the carcinogen administered increased. DMBA-DNA binding was found to increase with the increasing age of the rat. Nevertheless, dietary selenium supplementation was effective in reducing DMBA binding to DNA in all ages examined. These data confirmed the ability of dietary selenium to inhibit the in vivo metabolism of DMBA under a variety of conditions.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1992

Selenium content and distribution in bovine and human milk from different regions of Poland.

Human milk and bulk cow's milk samples from 3 different areas of central Poland were analyzed for their Se content. Cow's milk specimens were also analyzed for Se distribution and GSH-Px activity. Mature human milk contained 34-68% more Se than bulk cow's milk obtained from analogous areas of central Poland. Comparison of literature values suggest, that human and cow's milk from vicinity of Warsaw and Piotrków Trubunalski were Se-adequate but milk from Siedlce area was Se-deficient. Glutathione peroxidase activity accounted for 25-31% of the total peroxidase activity of cow's milk. The majority of the Se was found in the whey fraction. It was suggested that the participation of the casein fraction in total milk selenium increased faster than milk Se content. Cow's milk obtained near Warsaw had a 2-times higher concentration of Se than in milk from Siedlce but the content of this microelement in the casein fraction (pellet) was 3-times higher.

Animals↗

PubMed1992

The influence of age and sex on selenium distribution and glutathione peroxidase activity in plasma and erythrocytes of selenium-adequate and supplemented rats.

The experiment was performed on Sprague-Dawley male rats weighting 203, 103 and 53 g, and female 99 g. Animals were fed for 2 weeks a diet containing 0.1 and 2.0 ppm of Se (Na2SeO3 added). It was observed that the daily Se intake per kg of BW is lowered with an increase in animals body weight. Se-supplementation caused a significant increase of Se content in plasma and red blood cells. The highest concentration of Se in plasma and in RBC was found in females. GSH-Px activity was higher in RBC of all male rats receiving a Se-supplemented diet, but not in females. In plasma these differences between Se-adequate and supplemented rats were significant in youngest male rats and in females. These results suggest that age and sex of rats affect the concentration of Se and GSH-Px activity in plasma and RBC of rats.

Age Factors↗