Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

t-Butyl alcohol (TBA) was administered in drinking water to F344/N rats and B6C3F1 mice for two years using 60 animals/dose/sex/species. Male rats received doses of 0, 1.25, 2.5, or 5 mg/ml and females received 0, 2.5, 5, or 10 mg/ml, resulting in average daily doses of approximately 85, 195, or 420 mg TBA/kg body weight for males and 175, 330, or 650 mg/kg for females. Ten rats per group were evaluated after 15 months. Male and female mice received doses of 0, 5, 10, or 20 mg/ml, resulting in average daily doses of approximately 535, 1,035, or 2,065 mg TBA/kg body weight for males and 510, 1,015, or 2,105 mg/kg for females. Survival was significantly reduced in male rats receiving 5 mg/ml, female rats receiving 10 mg/ml, and male mice receiving 20 mg/ml. Long-term exposure to TBA produced increased incidences of renal tubule adenoma and carcinoma in male rats; transitional epithelial hyperplasia of the kidney in male and female rats; follicular cell adenoma of the thyroid in female mice; and follicular cell hyperplasia of the thyroid and inflammation and hyperplasia of the urinary bladder in male and female mice. In addition, a slight increase in follicular cell adenoma or carcinoma of the thyroid (combined) in male mice may have been related to the administration of TBA.
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PMID:Toxicity and carcinogenicity of t-butyl alcohol in rats and mice following chronic exposure in drinking water. 749 31

Lead is a high-priority hazardous substance in humans and a renal carcinogen in adult rodents. This study assessed the carcinogenic potential and toxicity of gestational and lactational lead exposure in (C57BL/6NCr x C3H/HeN)F1 (hereafter called B6C3F1) mice. Effects of a renal tumor promoter [barbital sodium (BB)] on lead-initiated lesions were also studied. Pregnant female C57BL/6NCr mice (10-15/group) previously bred with C3H/HeN males were given lead acetate (0, 500, 750 and 1000 ppm lead) ad libitum in their drinking water, starting on gestation day 12 and continuing to 4 weeks postpartum. Offspring were then weaned and divided into same-sex groups of 23-25 and observed for a maximum of 112 weeks. Other groups received lead and then continuous BB (500 ppm) ad libitum in their drinking water from weaning onward. In control male offspring (0 lead/0 BB), renal proliferative lesions [(RPLs); defined as atypical tubular hyperplasia or tumor] occurred rarely (1 lesion-bearing mouse/23 mice examined, 4%) and did not include tumors. RPLs increased in a dose-related fashion with lead exposure (500 lead/0 BB, 4/25, 16%; 750 lead/0 BB, 6/25, 24%; 1000 lead/0 BB, 12/25, 48%) in male offspring and were often multiple. All lead-treated groups had renal tumors, including carcinoma, but these were most common at the highest dose (1000 lead/0 BB, 5/25). Lead-induced renal tumors arose in the absence of the extensive chronic nephropathy and lead inclusion bodies typically seen with lead carcinogenesis in rodents exposed chronically as adults. Postnatal BB exposure had no effect on RPL incidence (e.g., 1000 lead/500 BB, 8/25, 32%). Lead-treated female offspring also developed RPLs, including adenoma and carcinoma, but at a much lower rate than males. Thus, short-term lead exposure during the gestational/lactational period has carcinogenic potential in the mouse kidney.
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PMID:Renal tubular tumors and atypical hyperplasias in B6C3F1 mice exposed to lead acetate during gestation and lactation occur with minimal chronic nephropathy. 758 86

In order to elucidate the role of point mutation of the K-ras gene in the tumorigenetic process of lung tumors, an experimental model of lung lesions in mice induced by the administration of urethane was used. A total of 135 B6C3F1 male mice, 6 weeks old, were given urethane in the drinking water at 0, 6, 60, 600 or 1200 ppm, and were then killed after varying periods of time. The lung lesions were histologically characterized as hyperplasia, adenoma and adenocarcinoma. Point mutations in codons 12 and 61 of the K-ras gene were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by using dideoxy sequencing analysis. K-ras gene mutation was identified in 9 (23.7%) of 38 lesions classified as hyperplasia, 31 (46.3%) of 67 adenomas, and 3 (50%) of 6 adenocarcinomas. The most frequent mutation was an AT-to-TA transversion at the second base of codon 61 and this pattern accounted for 65% of the three mutant forms observed. These results suggest that the point mutation of K-ras gene is involved in all stages of mouse lung tumorigenesis, i.e., activation of this gene can also influence the later stages of lung lesions.
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PMID:Role of point mutation of the K-ras gene in tumorigenesis of B6C3F1 mouse lung lesions induced by urethane. 759 56

Exposure of male Balb/C mice to mainstream cigarette smoke for 4 months, starting 10 or 30 days before the administration of ethyl carbamate (0.3% in drinking water for 3 weeks), resulted in an up to 57.6% (P < 0.05) decrease of lung adenoma multiplicity. However, the number of ethyl carbamate-induced lung tumors was not significantly affected by exposure to cigarette smoke when ethyl carbamate was injected i.p. in single doses of 0.5 or 1.0 g/kg, irrespective of the different treatment schedules used, i.e. (a) 10 days before and 4 days after the ethyl carbamate injection; (b) throughout the experiment starting 10 days before the ethyl carbamate injection, and (c) until the end of the experiment, starting 30 days after the ethyl carbamate injection. Disulfiram (500 mg/kg), given by gavage 24 h and 1 h before the ethyl carbamate injection, decreased by 88.5% (P < 0.001) the multiplicity of lung adenomas but had no effect on tumorigenesis when administered after the carcinogen injection. Proadifen (SKF-525 A, 50 mg/kg) injected i.p. 24 h and 1 h before and 24 h and 48 h after the injection with ethyl carbamate tended to decrease the multiplicity of lung adenomas, but not to a significant extent. Furthermore, disulfiram given 24 h and 1 h before the i.p. administration of ethyl carbamate completely prevented its clastogenicity in mouse bone marrow. On the other hand, cigarette smoke, which was per se a weak clastogen in bone marrow erythroblasts, synergistically potentiated the clastogenic response to ethyl carbamate in a more than additive fashion.
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PMID:Effects of cigarette smoke and disulfiram on tumorigenicity and clastogenicity of ethyl carbamate in mice. 762 51

Retrospective analysis has been performed on 108 consecutive patients operated for primary hyperparathyroidism (HPT) at 75 to 85 years of age (mean 79 years). The preoperative serum calcium value averaged 2.99 mM, and six patients had hypercalcemic crisis. Psychic disturbances were seen in 60 patients (56%), 40% of whom demonstrated dementia. Skeletal and muscular complaints were registered in 29% and 19%, respectively, and only 6% were overtly asymptomatic. Cardiovascular diseases were presented by 69% of the patients, 13% had diabetes mellitus, and 26% were institutionalized prior to surgery. Bilateral neck exploration disclosed a single adenoma in 69%, which was of the oxyphil cell type in 13%, and water-clear (n = 3) or chief cell hyperplasia in 27%. The total glandular weight averaged 1085 mg. Altogether 72 patients operated on after 1980 demonstrated a perioperative (30-day) mortality of 1.4%; the corresponding morbidity of 8.7% mainly included infections as well as a vocal cord paralysis in one patient and two incisional hematomas. Analysis for mean 3.1 years postoperatively displayed reversal of hypercalcemia in 95% of the patients; 2.8% of those operated after 1980 had persistent disease. Symptoms seemed to be alleviated in 62%, with a similar rate attained in patients with dementia. Altogether 60 patients died from mainly cardiovascular diseases mean 4.2 years after the operation. Those succumbing the first postoperative year (n = 21) showed overrepresentation of cardiac diseases and diabetes mellitus. The results demonstrate prevalent psychic disturbances, oxyphil adenomas, and multiglandular parathyroid disease in elderly patients with primary HPT and favor rather liberal application of parathyroid surgery among these individuals.
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PMID:Surgery for sporadic primary hyperparathyroidism in the elderly. 772 53

It has been suggested that endogenous substances (known as ouabain-like factors, OLF), secreted from the central nervous system in response to salt and water retention, inhibit the cell membrane Na+/K+ pump in the renal tubules and reduce sodium reabsorption. However, by also acting upon vascular smooth muscle cells, they may induce cell Na+ and Ca++ accumulation, vasoconstriction and systemic hypertension. Recently, an endogenous Na+/K+ pump inhibitor was isolated from human plasma; this inhibitor is indistinguishable from the cardiac glycoside ouabain based on biochemical and immunological criteria. Its plasma concentration is close to the therapeutic range for ouabain (around 0.4 nmol/L). Since plant ouabain promotes natriuresis, vasoconstriction, and hypertension; endogenous ouabain may therefore control extracellular fluid volume and blood pressure. The highest plasma concentrations of endogenous ouabain and OLF were found in congestive heart failure, aldosterone producing adenoma, human and animal models of volume expanded hypertension (reduced renal mass and DOCA-salt hypertension), and in Milan hypertensive rats (MHS). Aldosterone antagonists (canrenone and canrenoate) exert both agonist and antagonist effects on the digitalis receptor site of the Na+/K+ pump. They are effective antihypertensive agents in animal models of hypertension sustained by OLF (reduced renal mass-Na+ and DOCA-salt hypertension in rats). Moreover, in a subgroup of essential hypertensives, 4 weeks of canrenoate administration reduced blood pressure, heightened red blood cell Na+/K+ pump activity, and antagonized ouabain-induced vasoconstriction. None of these effects was seen in the other hypertensives. These data suggest that aldosterone antagonists stimulate the Na+/K+ pump inhibited by endogenous ouabain and exert their antihypertensive action at least in part through this mechanism.
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PMID:Ouabain-inhibiting activity of aldosterone antagonists. 779 94

Dimethylitaconate (DMI) is one of phase II enzyme inducers suggesting a candidate for a tumor inhibitor. We tested the modifying effect of DMI on post-initiation stage of MNU induced gastric carcinogenesis in male Fischer 344 rats. Groups I and II administered N-methylnitrosourea (MNU) at a concentration of 100 ppm in the drinking water for 15 weeks. Group II was treated 0.5% DMI in the drinking water for 37 weeks after the MNU treatment. Groups III and IV were DMI alone and untreated control, respectively. DMI-treated animals showed hyperplastic changes in gastric epithelium and the incidence was 40% in the DMI alone group. MNU combined with DMI significantly increased the adenoma incidence compared with MNU alone group (P < 0.05). The concomitant administration of DMI showed a significant increase of adenocarcinoma incidence, which was 95% (P < 0.005) compared with MNU alone group (11.8%). The replicative DNA synthesis and the labelling index of bromodeoxyuridine, which are the indicators of proliferating activity, were increased in the stomach of DMI-treated rats compared with untreated control (P < 0.001 and P < 0.005, respectively). These results suggested that DMI has potent promoting potential in the post-initiation stage of gastric carcinogenesis of rats and its mechanisms are probably involved in the induction of cell proliferation including replicative DNA synthesis.
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PMID:Potent promoting activity of dimethylitaconate on gastric carcinogenesis induced by N-methylnitrosourea. 795 34

Recent evidence has suggested that the induction of DNA synthesis by nongenotoxic chemical carcinogens plays an important role in the formation of cancer. The present study examined the effect of a nongenotoxic carcinogen, phenobarbital, (PB) on the induction of DNA synthesis in preneoplastic foci and adenomas in B6C3F1 mice. Male mice were treated with diethylnitrosamine at 30 days of age. After 6 months, mice had both hepatic foci and adenomas. Mice were divided into three groups at random and treated with PB in the drinking water and examined for DNA labeling by autoradiography. Before sacrifice, each mouse received an osmotic minipump containing [3H] thymidine. Results showed a PB dose-dependent increase in DNA synthesis in hepatic foci. Adenomas were unresponsive to the DNA synthesis-enhancing effect of PB, maintaining a level of 20-25%. The normal surrounding liver showed an increase in DNA synthesis (10-15% labeling index) at the 7-day sampling, which returned to normal control levels by 28 and 45 days. The foci showed a heterogeneity in response, with some foci showing an increase (20-30% labeling index), and others maintaining control DNA synthesis levels (4-6% labeling index). These results show that preneoplastic foci in the mouse respond preferentially to the induction of DNA synthesis by PB, that this response is dose dependent, and that it is maintained as long as the treatment continues.
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PMID:Selective induction of DNA synthesis in mouse preneoplastic and neoplastic hepatic lesions after exposure to phenobarbital. 801 13

To investigate the possible role of dopamine, a catecholamine with natriuretic properties, in modulating the escape from the sodium-retaining effects of mineralocorticoids, we submitted six aldosterone-producing adenoma (APA) patients and six low-renin essential hypertensive patients to acute volume expansion by head-out water immersion with or without dopaminergic blockade by metoclopramide. Water immersion alone induced a marked, comparable natriuresis (P < 0.001) in both hypertensive groups where a slight reduction of already suppressed renin-angiotensin system and a marked stimulation of atrial natriuretic peptide was also observed (P < 0.03 and P < 0.002, respectively). Water immersion plus dopaminergic blockade by metoclopramide did not significantly affect the natriuresis observed during water immersion alone in APA patients; conversely, there was a blunted natriuretic response in low-renin hypertensives during water immersion plus metoclopramide, in comparison with that obtained during water immersion alone (P < 0.006). Furthermore, metoclopramide did prevent the suppression of plasma aldosterone levels produced by central volume expansion alone in low-renin hypertensives, although it did not affect plasma aldosterone levels during water immersion in APA patients. Our data suggest that dopaminergic blockade does not counteract the natriuretic ability of the other hemodynamic and humoral mechanisms involved in the escape phenomenon of APA patients, thus casting serious doubt on the possible role of dopamine in mediating the escape from the sodium-retaining effects of mineralocorticoids.
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PMID:Escape from the sodium-retaining effects of mineralocorticoids: is there a role for dopamine? 810 35

Among their biological properties, several oxysterols display a stronger toxicity towards tumor cells than towards normal cells. Water-soluble phosphodiesters of 7 beta-hydroxycholesterol (JB69 and XA29), that were proved to retain a specific antitumoral activity in vitro, have been recently developed, allowing in vivo studies. They have been assayed on transgenic mice expressing the Large T antigen of SV40 in their liver and developing systematically hepatocarcinoma within 8 months. We show that JB69 and XA29 administered intraperitoneally into transgenic mice, before the onset of adenoma, may prevent or delay the tumor development. Consequently, oxysterol derivatives might constitute new efficient prodrugs against naturally occurring tumors.
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PMID:Effect of oxysterol derivatives on the time course development of hepatocarcinoma in transgenic mice. 839 69


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