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J B Mason

Publications and source records attributed to J B Mason.

At least 37 records · Page 2Linked to original sources
PubMed1999

The effect of dietary folate on Apc and p53 mutations in the dimethylhydrazine rat model of colorectal cancer.

Dietary inadequacy of folate enhances and folate supplementation suppresses colorectal carcinogenesis in the dimethylhydrazine rat model. Folate is an essential factor for DNA methylation and the de novo biosynthesis of nucleotides, aberrations of which play important roles in mutagenesis. This study investigated whether the mutational hot spots of the Apc and p53 genes for human colorectal cancer are mutated in dimethylhydrazine-induced colorectal neoplasms and whether dietary folate can modulate mutations in these regions. Rats were fed diets containing 0, 2 (basal requirement), 8 or 40 mg folate/kg diet. Five weeks after diet initiation, dimethylhydrazine was injected weekly for 15 weeks. Mutations were determined by direct sequencing in 11 low and seven high grade dysplasias and 13 invasive adenocarcinomas. A total of six Apc mutations were found in four dysplastic and carcinomatous lesions: two in two low grade dysplasias, two in one high grade dysplasia and two in one adenocarcinoma. All mutations were single base substitutions, four of which were A:T-->G:C transitions. Five of the six mutations were located upstream from the region corresponding to the human APC mutation cluster region. Dietary folate had no effect on the frequency and type of Apc mutations. No mutations were detected in exons 5-9 of the p53 gene in neoplastic lesions. These data suggest that in the dimethylhydrazine rat model of colorectal cancer, the Apc gene is mutated in early stages, albeit to a lesser degree than observed in human colorectal cancer, whereas the mutational hot spot of the p53 gene for human colorectal cancer is not commonly mutated. Although the low frequency of Apc mutations and the small number of neoplasms studied in this study might have precluded our ability to observe modulatory effects of folate, dietary folate appears to have no significant effect on Apc and p53 mutations.

Animals↗
PubMed1999

Chronic alcohol consumption induces genomic but not p53-specific DNA hypomethylation in rat colon.

Alcohol consumption has been implicated as an etiologic agent in colorectal carcinogenesis, but the mechanism by which alcohol enhances the development of colorectal cancer is not yet known. Recent reports indicate that alcohol consumption can diminish cellular S-adenosylmethionine levels, thus possibly altering normal patterns of DNA methylation, a phenomenon that is mediated by S-adenosylmethionine and whose abnormalities are observed in colonic neoplasia. This study investigated the effect of chronic alcohol consumption on genomic DNA methylation of rat colonic epithelium and methylation of the p53 tumor suppressor gene, abnormalities of which have been implicated in colonic carcinogenesis. Two groups of rats (n = 10/group) were pair-fed either an alcohol-containing or an isocaloric control Lieber-DeCarli diet for 4 wk. The extent of genomic DNA methylation was assessed by incubating the extracted DNA with [(3)H]S-adenosylmethionine and Sss1 methyltransferase. Gene-specific methylation was assessed by using semiquantitative polymerase chain reaction (PCR). Tritiated methyl uptake by colonic DNA (which is inversely correlated with genomic methylation) from alcohol-fed rats was 57% less than that in control DNA (P < 0.05). However, gene-specific DNA methylation, both in the p53 gene (exons 5-8) and in the beta-actin gene, a control gene, did not differ between the two groups. In conclusion, this study indicates that chronic alcohol consumption produces genomic DNA hypomethylation in the colonic mucosa. This may constitute a means by which carcinogenesis is enhanced, although further studies are required to establish causality.

Animals↗
PubMed1998

A cross-sectional study of vitamin intake in postoperative non-small cell lung cancer patients.

BACKGROUND AND OBJECTIVES: This cross-sectional study of postoperative non-small cell lung cancer (NSCLC) patients examined possible effects of vitamin intake and folate status on disease-free survival. METHODS: Supplemental vitamin usage, dietary vitamin intake (Willett Food Frequency Questionnaire), red blood cell (RBC) folate, and serum folate concentrations were assessed in patients with a history of NSCLC. Exclusion criteria included factors that alter folate status or that are associated with altered nutritional habits: (1) evidence of cancer on history, physical, or chest radiograph; (2) tobacco, alcohol ingestion (>2 drinks/ day), or cancer treatment within 3 months; (3) use of folate antagonists; and (4) age <60 years. RESULTS: 36 subjects were evaluated. The median disease-free censored survival was 24 months (range 4-41). Nineteen of 36 patients (53%) reported vitamin supplementation. Vitamin users had a longer median censored survival compared with nonusers (41 months versus 11 months; P = 0.002). With adjustment for cancer stage, the association between RBC folate and censored survival (r = 0.35; P = 0.055) and between serum folate and censored survival (r = 0.32; P = 0.083) approached statistical significance. CONCLUSIONS: NSCLC patients who took vitamin supplements were more likely to be long-term survivors in the patients studied; a similar trend toward long-term survival was seen among patients with higher circulating folate concentrations.

Aged↗
PubMed1998

Protein-calorie malnutrition does not predict subtle vitamin K depletion in hospitalized patients.

OBJECTIVE: Recent studies suggest that subtle vitamin K depletion has far-reaching consequences. As this entity is not associated with prothrombin time elevation, it is important to determine whether alternate methods can help identify it. We investigated subtle vitamin K depletion in a hospital setting and determined whether protein calorie malnutrition predicts its presence. DESIGN, SETTING, SUBJECTS: Using a high-pressure liquid chromatography (HPLC) assay of plasma phylloquinone and a food frequency questionnaire for phylloquinone intake, we examined the phylloquinone status of 27 hospitalized patients with normal coagulation parameters, no liver disease, and no recent warfarin use. We assessed protein-calorie nutritional status with Reilly's criteria and anthropometrics. RESULTS: 51% of patients (95% CI = 31% to 70%) had evidence of subtle vitamin K depletion as defined by a subnormal plasma phylloquinone concentration. Patients whose phylloquinone intake was less than the Recommended Daily Allowance (RDA) over the preceding year had lower plasma phylloquinone concentrations when compared to other patients: median (range) 0.106 nmol/l (0.022-0.461) versus 0.301 nmol/l (0.067-3.928), respectively (P = 0.023). Plasma phylloquinone concentrations were no different, however, between well-nourished and malnourished patients: median (range) 0.245 nmol/l (0.022-0.522) versus 0.188 nmol/l (0.067-3.928), respectively (P=0.782). CONCLUSIONS: Subtle vitamin K depletion is common among hospitalized patients and protein-calorie malnutrition does not predict its presence.

Adult↗
PubMed1998

Bioavailability of phylloquinone from an intravenous lipid emulsion.

This randomized, controlled study evaluated the bioavailability of phylloquinone from an intravenous lipid emulsion. A mild vitamin K deficiency was induced in 12 healthy adult men and women by dietary restriction of phylloquinone (40 microg/d, days 1-11) and by administration of warfarin (1.0 mg/d, days 5-11). On day 11, subjects received a 500-mL intravenous solution of either lipid or saline, both of which contained 154 microg phylloquinone. Bioavailability was assessed by serial measurements of plasma phylloquinone, vitamin K1-2,3-epoxide. PIVKA-II (proteins induced by vitamin K absence or antagonists-II), and percentage undercarboxylated osteocalcin. As a result of vitamin K deficiency and minidose warfarin, vitamin K1-2,3-epoxide, PIVKA-II, and percentage undercarboxylated osteocalcin increased significantly between days 1 and 11 (P = 0.05, 0.016, and 0.001, respectively). With the infusions, plasma phylloquinone increased in both groups (P = 0.001). After the infusions vitamin K,-2,3-epoxide decreased in both groups (P = 0.002). Changes in plasma phylloquinone and vitamin K1-2,3-epoxide were no different in the two groups (mean areas under the curves +/- SEM: 116+/-13 nmol x h/L for the saline group and 102+/-20 nmol x h/L for the lipid group for phylloquinone; 38.6+/-7.5 nmol x h/L for the saline group and 31.3+/-9.0 nmol x h/L for the lipid group for vitamin K1-2,3-epoxide). PIVKA-II decreased significantly from baseline values (P = 0.005) in both groups after the infusions. Intravenous lipid reversed the effects of minidose warfarin and of dietary restriction of phylloquinone on hemostasis and vitamin K nutritional status. This reversal was no different from that seen with the infusion of phylloquinone in a saline solution.

Adult↗
PubMed1998

Colonic mucosal concentrations of folate correlate well with blood measurements of folate status in persons with colorectal polyps.

BACKGROUND: Estimates of habitual dietary folate intake are known to be imprecisely correlated with systemic measures of folate status. Furthermore, measurements of blood folate concentrations may not accurately reflect the concentration of folate in tissues of interest. This issue is important for assessing folate status in the colorectal mucosa because low dietary intake or blood concentrations of folate are associated with an increased risk of colorectal neoplasia. OBJECTIVE: We examined whether conventional measures of folate in blood and a more sensitive, inverse indicator of systemic folate status, serum homocysteine, accurately reflected folate concentrations in human colonic mucosa obtained by endoscopic biopsy. DESIGN: In 30 persons with colorectal polyps, blood samples were taken and biopsies of normal rectosigmoid mucosa performed at the time of colonoscopic polypectomy. Serum, red blood cell, and colonic mucosal folate and serum homocysteine concentrations were measured. RESULTS: Serum and red blood cell folate and serum homocysteine concentrations accurately reflected colonic mucosal folate concentrations; among these, serum homocysteine correlated best with mucosal concentrations. Folate concentrations in the normal rectosigmoid mucosa were significantly lower in persons with adenomatous polyps than in those with hyperplastic polyps (P=0.04). Conventional measures of systemic folate status were not significantly lower in those with adenomas, although serum homocysteine was mildly elevated (P=0.04). CONCLUSIONS: Our data underscore the ability of systemic measures of folate status, particularly serum homocysteine, to reflect folate concentrations in the colonic mucosa. Nevertheless, future studies that examine the ability of folate to modulate colorectal carcinogenesis may benefit from direct measurement of folate in the colon.

Adenoma↗
PubMed1998

Folate depletion impairs DNA excision repair in the colon of the rat.

BACKGROUND/AIMS: Diminished folate status appears to promote colonic carcinogenesis by, as of yet, undefined mechanisms. Impaired DNA repair plays a significant role in the evolution of many colon cancers. Since folate is essential for the de novo synthesis of nucleotides and since folate depletion has previously been associated with excessive DNA strand breaks, it was hypothesised that folate depletion may impair DNA repair. Studies were therefore performed to examine whether folate depletion affects the two major categories of DNA repair. METHODS: Study 1: eight weanling male Sprague-Dawley rats were fed on diets containing either 0 or 8 mg folate/kg diet with 1% succinylsulphathiazole for four weeks. After viable colonocytes had been harvested, DNA excision repair was evaluated by a single cell gel electrophoresis assay. Study 2: eighteen animals were fed on similar diets for five weeks. Also in study 2, 18 additional rats were fed on the same defined diet without succinylsulphathiazole for 15 weeks. Weekly injections with the procarcinogen, 1,2-dimethylhydrazine (20 mg base/kg), were administered to the latter group of animals. Five microsatellite loci from different chromosomes were investigated for instability in hepatic and colonic DNA. RESULTS: In study 1, a significantly retarded rate of DNA excision repair was observed in the folate deficient colonocytes compared with controls (p < 0.05). In study 2, there was no evidence of instability at the five microsatellite loci associated with either short or long term folate depletion. CONCLUSIONS: Folate deficiency impairs DNA excision repair in rat colonic mucosa; a similar degree of deficiency, even when administered in conjunction with a colonic carcinogen, did not produce evidence of a widespread defect in mismatch repair.

1,2-Dimethylhydrazine↗
PubMed1997

Folate deficiency in rats induces DNA strand breaks and hypomethylation within the p53 tumor suppressor gene.

Folate is essential for the de novo biosynthesis of purines and thymidylate, and is an important mediator in the transfer of methyl groups for DNA methylation. Folate deficiency, therefore, could contribute to abnormal DNA integrity and methylation patterns. We investigated the effect of isolated folate deficiency in rats on DNA methylation and DNA strand breaks both at the genomic level and within specific sequences of the p53 tumor suppressor gene. Our data indicate that folate deficiency induces DNA strand breaks and hypomethylation within the p53 gene. Such alterations either did not occur or were chronologically delayed when examined on a genome-wide basis, indicating some selectivity for the exons examined within the p53 gene. Folate insufficiency has been implicated in the development of several human and experimental cancers, and aberrations within these regions of the p53 gene that were examined in this study are thought to play an integral role in carcinogenesis. The aforementioned molecular alterations may therefore be a means by which dietary folate deficiency enhances carcinogenesis.

Animals↗
PubMed1996

DNA hypomethylation in inflammatory arthritis: reversal with methotrexate.

This study investigated whether methotrexate, by interrupting the methyl transfer function of folate, can induce genomic DNA hypomethylation in patients with inflammatory arthritis. Consecutive subjects with inflammatory arthritis (rheumatoid or psoriatic), who were taking methotrexate (n = 7) or other medications (n = 6), and control subjects, either healthy or with osteoarthritis and taking nonsteroidal anti-inflammatory agents only (n = 9) were recruited. The methylation status of genomic DNA from peripheral blood mononuclear cells was determined. Plasma levels of folate, B12, and pyridoxal-5'-phosphate (PLP), all of which are involved in biologic methylation, were also examined. The extent of genomic DNA methylation was lowest in subjects with inflammatory arthritis who were not taking methotrexate, highest in subjects with inflammatory arthritis who were taking methotrexate, and intermediate in control subjects (p < 0.05). Plasma levels of folate and B12 were similar among the three groups. The mean plasma PLP level in subjects with inflammatory arthritis was 33% lower than that in control subjects (p = 0.04). No significant correlation between genomic DNA methylation and folate, B12, and PLP levels was observed. These data do not support the hypothesis that methotrexate induces genomic DNA hypomethylation. However, these data indicate that inflammatory arthritis is associated with genomic DNA hypomethylation that is reversed with methotrexate. Future studies using a larger number of subjects are warranted to confirm these findings.

Adult↗
PubMed1996

Folate synthesized by bacteria in the human upper small intestine is assimilated by the host.

BACKGROUND & AIMS: Some intestinal flora are known to synthesize folate. The aim of this study was to determine whether folate synthesized by small intestinal flora is assimilated by the human host. METHODS: Subjects with atrophic gastritis and healthy volunteers were studied before and after omeprazole administration. A double-lumen perfusion tube was placed in the duodenum. 3H-labeled P-aminobenzoic acid, a precursor substrate for bacterial folate synthesis, was perfused. Downstream intestinal aspirates and a 48-hour urine collection were obtained. RESULTS: Atrophic gastritis and omeprazole administration were associated with increases in duodenal pH and in small intestinal flora. Bacterially synthesized folates were isolated from the intestinal aspirates. Tritiated 5-methyltetrahydrofolate, a major metabolite of folate, was isolated from the urine of omeprazole-treated subjects in greater quantities than from drug-free subjects (P<0.01); the quantity of tritiated 5-methyltetrahydrofolate in the urine of the subjects with atrophic gastritis was similarly elevated. CONCLUSIONS: (1) Mild bacterial overgrowth caused by atrophic gastritis and administration of omeprazole are associated with de novo folate synthesis in the lumen of the small intestine; (2) the human host absorbs and uses some of these folates; and (3) the contribution to folate nutriture from this source remains unclear.

4-Aminobenzoic Acid↗
PubMed1996

Setting and evaluating the energy content of emergency rations.

This paper examines the setting and evaluation of emergency rations for refugees and displaced people. After defining the purpose for which rations are designed, the variables affecting their quantification are discussed. The debate concerning the use of one as opposed to a range of energy levels for different populations is highlighted in a review of recent proposals for ration levels. It is demonstrated that up to a twofold range occurs if different combinations of the main parameters are used. This has important implications for the large-scale provision of food. The use of one figure for the setting and evaluation of rations for all populations is inappropriate; figures should be set according to specific context and need. To achieve this, a practical two-stage approach is proposed. Stage 1, probably a desk exercise, uses pre-calculated 'look-up' tables which provide energy values for each country. These figures are for immediate use as 'rule-of-thumb' estimates, based on clearly defined parameters. The second stage involves refining the values using improved information on local conditions collected by field assessment.

Activities of Daily Living↗
PubMed1996

Nutrition chemoprevention of gastrointestinal cancers: a critical review.

Various strategies utilizing specific dietary factors have been investigated for their ability to modulate the development of several cancers of the gastrointestinal tract. The effects of fat, red meat, fiber, fruits and vegetables, and alcohol on colorectal carcinogenesis have been reasonably well defined. Folate, selenium, and omega-3 fatty acids are rapidly emerging as important agents in nutrition chemoprevention, while the role of antioxidant vitamins and calcium is less certain. Although recent intervention studies from China have suggested a protective role of certain vitamins and minerals for esophageal and gastric cancers, further data from prospective randomized intervention studies are needed. Until more firm data are available, the dietary recommendations provided by the American Cancer Society and the National Cancer Institute are appropriate guidelines.

American Cancer Society↗