Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a study to determine the effect of saturation of fats on their ability to stimulate cholecystokinin (CCK) release six normal volunteers ate five test meals containing different fats with intervals of 1 week. Plasma CCK levels were measured by a specific radioimmunoassay and the gallbladder volume was calculated from ultrasound measurements. The sodium salt of the monounsaturated fatty acid oleic acid (3.5 g) produced a significantly greater integrated CCK response than that of the saturated fatty acid stearic acid (mean [SEM] 103 [41] vs 8[41] pmol.l-1.min). The gallbladder contracted to 42 (3)% of its initial volume after oleate but remained at 89 (8)% of its initial volume after stearate. Integrated CCK responses to dietary triglycerides (30 g) also differed significantly according to the degree of saturation--277 (58) pmol.l-1.min after corn oil (predominantly diunsaturated), 143 (14) pmol.l-1.min after olive oil (predominantly monounsaturated), and 44 (12) pmol.l-1.min after suet (predominantly saturated). The finding that unsaturated fats are stronger stimulants of CCK release than saturated fats may explain the promotion of pancreatic carcinogenesis in rats by unsaturated but not saturated fats and may support the role of CCK in this effect.
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PMID:Saturation of fat and cholecystokinin release: implications for pancreatic carcinogenesis. 257 43

The goal of this study is to show the relationship of inhaled Pu particle distribution and alveolar-bronchiolar target-cell response with respect to the formation of pulmonary carcinoma. The proliferation of type 2 alveolar epithelium and nonciliated bronchiolar epithelium appears critical in the induction of lung tumors associated from inhaled 239PuO2. Female, Wistar rats were either sham-exposed (40 rats) or given a single inhalation to 169Yb-239PuO2 (99 rats, ILB, 3.9 +/- 1.2 kBq) and examined at 20 time intervals from 1 day to 700 days postexposure for Pu particle distribution in airways by SEM quantitative autoradiography and for cell labeling with tritiated thymidine. Initially, deposited Pu particles were rapidly cleared from the surface of the trachea, bronchi, and bronchioles within a few days. Thereafter, about 5 times more alpha track exposure to the bronchiolar epithelium was delivered from Pu particles found in peribronchiolar alveoli than from Pu particles being cleared from bronchiolar surfaces. Exposure of bronchiolar epithelium at later times was due mostly to the formation of peribronchiolar Pu particle aggregates. A maximal increase in labeled alveolar wall cells was seen at 60 days after exposure, decreasing gradually to control levels by 400 days. Cell labeling in focal alveolar regions of Pu aggregation was about 5 fold higher. Increased bronchiolar epithelium labeling appeared in two phases. The first phase was seen 15 days after exposure, associated with initial deposition and clearance of Pu particles. The second phase slowly reached a maximum at 250 days and was associated with peribronchiolar Pu aggregate formation. The temporal-spatial dose-distribution pattern for inhaled Pu particles is an important aspect of Pu-induced pulmonary carcinogenesis.
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PMID:Tritiated thymidine-labeled bronchioloalveolar cells and radiation dose following inhalation of plutonium in rats. 280 95

The mechanism of the genotoxicity and metabolism of benzene (BZ) was investigated by using a free-radical scavenger, dimethyl sulfoxide (DMSO), to investigate the free radical mechanism in BZ metabolism. The presence of chromosomal breakage expressed as micronuclei (MN) in bone marrow polychromatic erythrocytes (PCE) and the presence of several BZ metabolites in the urine were monitored. Adult male ICR mice were exposed orally to DMSO after oral exposure to BZ (440 mg/kg b.w.). DMSO was administered either in different concentrations (1.25, 3.75 or 12.5% given at a volume of 0.01 ml/gm b.w.) or at different intervals after BZ exposure (1, 3 or 5 h). Each group consisted of five mice. It was found that the BZ-induced MN frequency was reduced by DMSO from 48.8 +/- 5.6 (SEM) to 2.6 +/- 0.7 per 1000 PCE when DMSO (12.5%) was administered at 1 h after BZ exposure (P less than 0.01), to 3.4 +/- 0.8 at 3 h (P less than 0.01) and to 36.2 +/- 12.1 at 5 h (P less than 0.01). The reduction of the clastogenic effect of BZ by DMSO was also dependent upon the DMSO doses. The MN frequency was significantly reduced from 48.8 +/- 5.6 to 29.4 +/- 10.9 with 1.25% DMSO (P less than 0.01) to 20 +/- 7.6 with 3.75% (P less than 0.01) and to 2.6 +/- 0.7 with 12.5% DMSO (P less than 0.01). The presence of different metabolites of BZ such as hydroquinone, catechol, trans-trans muconic acid (MA, the oxidized form of trans-trans muconaldehyde, ttM), and total and conjugated phenol was evaluated in the urine of the exposed mice using HPLC. Among these metabolites, the quantity of MA was found to have the closest positive correlation with the MN frequency (P less than 0.007). Phenol but not the other monitored metabolites was also positively correlated with MN frequency (P less than 0.03). Thus, our data show that the formation of genotoxic metabolites from BZ probably involves hydroxyl radicals and ttM as well as phenol are likely to be responsible for the clastogenic effect of benzene in vivo.
Carcinogenesis 1989 Mar
PMID:Effect of dimethyl sulfoxide on the genotoxicity and metabolism of benzene in vivo. 292 92

The main adduct of cis-diamminedichloroplatinum(II) (cis-Pt) with DNA, cis-[Pt(NH3)2(dGpdG)], was administered i.p. to rats. Urine was collected daily for 4 days. The adduct was purified by a weak cation exchanger and quantitated by HPLC with UV detection. The recovery of the adduct was 30.0 +/- 7.0% (mean +/- SEM). The main reason for the low recovery was the chemical instability of cis-[Pt(NH3)2 (dGpdG)] in urine as shown in an in vitro incubation. Adjusted for this instability the recovery in urine was greater than 70% of the dose. When cis-Pt-DNA (the molar ratio of cis-Pt to nucleotide = 1:50) was administered i.p. to rats only 1.25 +/- 0.23% of platinum was excreted in urine in the form of cis-[Pt(NH3)2(dGpdG)] and cis-[Pt(NH3)2(dApdG)] during the first 4 days. If the removal of the cis-Pt-DNA adducts from human tissues is to be followed, their possible slow excretion and chemical instability in urine needs to be considered.
Carcinogenesis 1988 Oct
PMID:Excretion kinetics of the DNA adducts of cis-diamminedichloroplatinum(II) formed in vitro in rat urine. 316 53

Nitrosodimethylamine (NDMA) is a potent carcinogen in a wide variety of animal species. In experimental animals, dimethylamine and nitrite, precursors of NDMA, are found in gastric fluid where the acidic conditions are suitable for formation of nitrosamines. In this study we measured the concentrations of mono-, di- and trimethylamine (MMA, DMA and TMA) in gastric fluid from humans, rats, dogs and ferrets, as well as in saliva, blood and urine from humans. Human gastric fluid contained 3.7 +/- 0.4 (SEM) nmol/ml MMA, 12.6 +/- 1.4 nmol/ml DMA and 2.0 +/- 0.4 nmol/ml TMA. MMA, DMA and TMA concentrations in human gastric fluid were similar to those present in human saliva and blood, but were much lower than those present in human urine. The concentrations of these amines in human gastric fluid were lower than those measured in gastric fluid from experimental animals. When we added sodium nitrite to human gastric fluid, NDMA was formed. We have shown that DMA is normally present in human gastric fluid, and that it can be nitrosated to form NDMA.
Carcinogenesis 1988 Jan
PMID:Mono-, di- and trimethylamine in human gastric fluid: potential substrates for nitrosodimethylamine formation. 333 43

Measurement of N-nitroso compounds in gastric juice by different methods has given conflicting results. In order to resolve this controversy, we have assessed endogenous nitrosation by the independent N-nitrosoproline excretion test in subjects who had previously undergone gastric juice analysis by one of these methods. Ten Polya gastrectomy, 10 pernicious anaemia and nine matched control subjects were fed 380 mg of nitrate in beetroot juice and 500 mg proline. N-nitrosoproline (N-Pro) synthesised intragastrically from these precursors, and quantitatively excreted by the kidneys, was measured in 24 hour urine samples (collection checked by creatinine clearance). N-Pro excretion (mean +/- SEM) was reduced (p less than 0.01) in pernicious anaemia (1.1 +/- 0.8 ng/day) compared with matched control (18.0 +/- 7.2 ng/day), and also tended to be lower (NS) in polya gastrectomy (3.2 +/- 2.3 ng/day). Twenty four hour intragastric pH was monitored on a separate occasion in 23 of the 29 subjects; 13 were hypoacidic (pH greater than 4 greater than 50% of 24 hours) and 10 were acidic. N-Pro yields were reduced (p less than 0.01) in the hypoacidic group (0.9 +/- 0.6 ng/day) compared with the acidic group (17.9 +/- 6.6 ng/day), and N-Pro was negatively associated with mean intragastric pH (tau = -0.53, p = 0.001). We conclude that endogenous synthesis of this specific N-nitroso compound is favoured by low rather than high pH. These results are concordant with those previously reported in gastric juice from the same subjects and suggest that nitrosation is chemically rather than bacterially mediated, contrary to the nitrosamine hypothesis of gastric carcinogenesis.
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PMID:Urinary N-nitrosoproline excretion: a further evaluation of the nitrosamine hypothesis of gastric carcinogenesis in precancerous conditions. 355 92

Zinc and vitamin A are known to interact, and deficiencies have been associated with carcinogenesis in experimental animals and humans. Since we previously have demonstrated decreased plasma zinc and vitamin A levels in patients with esophageal cancer, we wished to examine endoscopically obtained epithelial tissue for vitamin A and zinc content. This was not feasible for vitamin A, but using newly developed techniques for zinc analysis of small tissue samples, we measured esophageal epithelial zinc as well as plasma zinc and plasma vitamin A in 21 patients with esophageal cancer, 17 patients with esophagitis, and 12 normals. Mean plasma zinc in the esophageal cancer group (56 +/- 3 micrograms/dl) (mean +/- SEM) was significantly less than in the esophagitis group (72 +/- 5 micrograms/dl) and the normals (78 +/- 5 micrograms/dl). Mean plasma vitamin A in the esophageal cancer group (32 +/- 3 micrograms/dl) was significantly less than the esophagitis group (57 +/- 4 micrograms/dl) or the normals (58 +/- 5 micrograms/dl). There was no significant difference in tissue zinc content (measured as micrograms zinc/g wet weight of tissue, mean +/- SEM) among cancerous tissue (57 +/- 5 micrograms/g) and adjacent normal tissue (61 +/- 4 micrograms/g), esophagitis tissue (66 +/- 6 micrograms/g) and adjacent normal tissue (61 +/- 6 micrograms/g), or normal esophageal tissue (59 +/- 6 micrograms/g). We conclude that deficiencies of zinc or vitamin A may be cofactors in the induction of human esophageal cancer, but a mechanism cannot be accounted for by differences in epithelial zinc content.
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PMID:Esophageal zinc content in human squamous esophageal cancer. 358 28

In vitro organ culture of the hamster's trachea was improved and applied to a carcinogenesis research. The rotary culture enabled explants of tracheal epithelium to survive more than 8 weeks. The study was composed of 2 kinds of culture; untreated and treated with carcinogens. In the untreated culture, Eagle MEM medium had the same culture effect as RPMI 1640 medium. With prolongation of culture time (particularly longer than 5 weeks), irreversible degenerative changes appeared in epithelial cells. Culture for 4 weeks was usually thought to be appropriate for experimental research. In the treated culture, the effect of benzo-(a) pyrene (B(a)P) and B(a)P + cigarette smoking condensate-neutral fraction (CSC-NF) on tracheal epithelium was investigated with light and electron microscopies (TEM and SEM) and autoradiography. Atypical hyperplasia with or without lesions suggesting carcinoma in situ was induced by B(a)P + CSC-NF more evidently and frequently than by B(a)P alone. The present findings corroborated the cocarcinogenetic effect of CSC-NF.
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PMID:In vitro alterations of tracheal epithelium of hamsters by carcinogens in organ culture. 361 62

The concentrations of nitrate, nitrite, N-nitroso compounds and bacteria were measured in 96 samples of fasting gastric juice, pH 0.90-8.50, obtained from 56 individuals just before or at various times (8 days - 1 year) after gastric operation. The mean pH of the post-operative samples [4.66 +/- 0.39 (SEM)] was significantly higher than that of the pre-operative ones [3.29 +/- 0.33 (SEM)]. A positive correlation with pH was observed for the concentrations of total and nitrate-reducing bacteria (median values 5.0 X 10(5) organisms/ml and 9.2 X 10(4) organisms/ml, respectively, for samples with pH greater than or equal to 1.2 X 10(3) organisms/ml and 0 organisms/ml, respectively, for samples with pH less than or equal to 2.5) and nitrite [mean values 22.5 +/- 3.1 (SEM) microM and 3.20 +/- 0.5 (SEM) microM for samples with pH greater than or equal to 6.5 and pH less than or equal to 2.5, respectively]. No correlation with pH was seen for the concentrations of nitrate [mean value 0.48 +/- 0.06 (SEM) mM] or N-nitroso compounds [mean value 0.30 +/- 0.06 (SEM) microM]. The concentrations of bacteria and nitrite, although increased in hypochlorhydric individuals, were lower than those reported for corresponding individuals in other, primarily British, studies. It is suggested that the relatively low concentrations of nitrite observed in our hypochlorhydric population may account for the absence of elevated concentrations of N-nitroso compounds and that the latter phenomenon may be related to the relatively low frequency of gastric cancer in Greece.
Carcinogenesis 1985 Aug
PMID:Studies in gastric carcinogenesis. II. Absence of elevated concentrations of N-nitroso compounds in the gastric juice of Greek hypochlorhydric individuals. 401 83

As the relative resistance of rat caecum to chemical carcinogens could reflect its luminal environment, caecal mucosa was exposed to the distal faecal stream in male Sprague-Dawley rats (n = 50) previously treated with azoxymethane (total dose 90 mg/kg sc). After colonic transection at the pelvic brim, the caecum was inserted isoperistaltically between colocaecal and caecorectal anastomoses (n = 30); an ileocolic anastomosis restored intestinal continuity. Controls (n = 20) had transection and reanastomosis at equivalent points of the bowel, plus caecotomy and resuture. Caecal crypt cell production rate, as determined stathmokinetically at 28 weeks, was not consistently affected by transposition. No tumors developed in either transposed or orthotopic caecum, apart from three suture-line tumours found at the caecotomy site in controls. The colonic tumour yield in controls (1.4 +/- 0.3 per rat : mean +/- SEM) matched that after transposition (1.5 +/- 0.2), but anastomotic tumours were twice as common after transposition (p less than 0.05) and rectal tumours were increased four-fold (p less than 0.05). The caecum remains resistant to carcinogenesis despite transposition to a distal colonic environment. Local epithelial defence mechanisms are more important than luminal contents in maintaining this resistance.
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PMID:Distal transposition of rat caecum does not render it susceptible to carcinogenesis. 401 36


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