Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ferric nitrilotriacetate (Fe-NTA) induced dose- and time-dependent mutation of V79 Chinese hamster cells to 6-thioguanine resistance. It also caused dose-related inhibition of metabolic cooperation. However, no significant induction of chromosome aberrations was detected in cells treated with Fe-NTA up to 100 micrograms Fe/ml of the drug even after treatment for 3 days. Our results indicate that Fe-NTA has mutagenic effects on V79 cells and inhibitory effects on cell--cell communication, and these effects may contribute to NTA-Fe-induced neoplastic transformation of mammalian cells.
Carcinogenesis 1990 Feb
PMID:Mutagenic effects of ferric nitrilotriacetate (Fe-NTA) on V79 Chinese hamster cells and its inhibitory effects on cell-cell communication. 230 53

A significant increase of 8-hydroxydeoxyguanosine (8-OH-dG) was observed in the kidney DNA of rats given a renal carcinogen, the ferric complex of nitrilotriacetate (Fe-NTA) by single i.p. injection. By contrast, non- or weakly carcinogenic compounds, aluminum-nitrilotriacetate complex (Al-NTA), non-complexed NTA (Na2NTA) and ferric chloride had no effect on 8-OH-dG production in the kidney DNA. These results suggest the involvement of active oxygen radicals in Fe-NTA carcinogenesis.
Carcinogenesis 1990 Feb
PMID:Formation of 8-hydroxydeoxyguanosine (8-OH-dG) in rat kidney DNA after intraperitoneal administration of ferric nitrilotriacetate (Fe-NTA). 230 61

Reactivities of Fe3+ chelates of aminopolycarboxylic acids with DNA were investigated by the DNA-sequencing technique using 32P 5'-end-labeled DNA fragments obtained from the human c-Ha-ras-1 protooncogene, and the reaction mechanism was studied by electron spin resonance spectroscopy. Ferric nitrilotriacetate (Fe3+-NTA) plus hydrogen peroxide caused strong DNA cleavage in the presence of albumin. No or little DNA cleavage was observed with ferric chloride or Fe3+ chelates of other aminopolycarboxylic acids tested in the presence of hydrogen peroxide. The DNA cleavage by Fe3+-NTA plus hydrogen peroxide without piperidine treatment occurred at positions of every nucleotide although a specific cleavage was observed, whereas cleavages at the positions of guanine and thymine increased predominantly with piperidine treatment. Electron spin resonance studies using free radical traps demonstrated that of Fe3+ chelates of aminopolycarboxylic acids, Fe3+-NTA was the most effective catalyst in hydrogen peroxide-derived production of hydroxyl radicals under our conditions. The results suggest that Fe3+-NTA catalyzes the decomposition of hydrogen peroxide to produce hydroxyl radicals, which subsequently cause the strong base alterations of guanine and thymine, and deoxyribose-phosphate backbone breakages. The possibility that the Fe3+-NTA-induced DNA damage is the initiation and/or promotion of carcinogenesis by Fe3+-NTA is discussed.
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PMID:Hydroxyl radical production and human DNA damage induced by ferric nitrilotriacetate and hydrogen peroxide. 282 34

The effects of trisodium nitrilotriacetate monohydrate (Na3 NTA.H2O) nitrilotriacetic acid (H3NTA) and ammonium chloride (NH4Cl) on two-stage urinary bladder carcinogenesis were examined. Carcinogenesis was initiated by administration of 0.2% N-bis (2-hydroxypropyl)-nitrosamine (DHPN) to male Wistar rats in the drinking water for 2 weeks, and then the animals were treated with basal diet containing Na3NTA.H2O, Na3NTA.H2O plus NH4Cl, H3NTA, H3NTA plus NH4Cl, or without these chemicals for 28 weeks. Na3NTA.H2O increased significantly the resultant incidence of neoplastic and preneoplastic lesions of the urinary bladder. Moreover, treatment with Na3NTA.H2O, without the initiation, itself induced papillary or nodular (PN)-hyperplasia. H3NTA produced only a slight increase in the incidence of preneoplastic urinary bladder lesions (PN-hyperplasia) in rats initiated by DHPN, and this was not statistically significant. Elevation of both pH and sodium ion concentration in the urine were correlated with promotion of tumor development. These data showed that Na3NTA.H2O was more effective than H3NTA with regard to promoting potential, and that changes in both urinary pH and concentration of sodium played important roles in enhancement of urinary bladder tumorigenesis by these chemicals.
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PMID:Effects of trisodium nitrilotriacetate monohydrate, nitrilotriacetic acid and ammonium chloride on urinary bladder carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl) nitrosamine. 320 20

The dose-dependent effect of trisodium nitrilotriacetate monohydrate (Na3.NTA.H2O) as a promoter in 2-stage carcinogenesis in the urinary bladder of male Wistar rats was investigated. Carcinogenesis was initiated by administration of 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in the drinking water for 4 weeks, then Na3.NTA.H2O was given at 1%, 0.5% and 0.3% in the diet for 28 weeks, and rats were killed in week 32. The incidences and numbers of preneoplastic lesions [papillary or nodular hyperplasia (PN hyperplasia)] in rats treated with 0.3% to 1% Na3.NTA.H2O increased progressively with increasing concentration of Na3.NTA.H2O. The incidences of papillomas in rats treated with 1% and 0.5% Na3.NTA.H20 in the diet and the incidence of transitional cell carcinoma (TCC) of the urinary bladder in the rats treated with 1% Na3.NTA.H2O (P less than 0.05) were significantly higher than those in rats treated with BBN only. Administration of various doses of Na3.NTA.H2O without BBN did not cause any histological changes (PN hyperplasia, papilloma or TCC) in the urinary bladder. These findings showed that Na3.NTA.H2O is a potent promoter of urinary bladder carcinogenesis initiated by BBN in rats, and that its effect is dose-dependent.
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PMID:Dose-dependent promoting effect of trisodium nitrilotriacetate monohydrate on urinary bladder carcinogenesis in Wistar rats pretreated with N-butyl-N-(4-hydroxybutyl)nitrosamine. 393 79

The development of renal tumors was examined in rats given 1000 p.p.m. N-ethyl-N-hydroxyethylnitrosamine (NEELA) and then 30 000, 10 000 or 3000 p.p.m. of trisodium nitrilotriacetate monohydrate (Na3 X NTA X H2O) in their food. The incidences of renal tumors in rats treated with NEELA for 2 weeks and then 30 000, 10 000 and 3000 p.p.m. Na3 X NTA X H2O for 30 weeks were 100, 86 and 22%, respectively, while they were 16 and 0% in rats treated with NEELA or 30 000 p.p.m. Na3 X NTA X H2O alone. Na3 X NTA X H2O at 30 000 or 10 000, but not 3000 p.p.m., also increased the size and number of renal tumors in rats treated with NEELA, and Na3 X NTA X H2O at 30 000 p.p.m., but not 10 000 or 3000 p.p.m., also induced hydronephrosis in rats irrespective of whether they were treated with NEELA. Thus, Na3 X NTA X H2O has a dose-related effect on the kidney.
Carcinogenesis 1985 Jun
PMID:Dose-related effect of trisodium nitrilotriacetate monohydrate on renal tumorigenesis initiated with N-ethyl-N-hydroxyethylnitrosamine in rats. 400 78

The effects of the renal carcinogen ferric nitrilotriacetate (Fe-NTA) on kidney DNA of male F344 rats were studied to determine whether bulky DNA oxidation products (putative intrastrand crosslinks) could be detected by 32P-postlabeling in the target organ of carcinogenesis. Rats (10-11 weeks old) were given a single dose of Fe-NTA (15 mg Fe/kg body weight) i.p. at 3:00 pm. After 5 h, renal DNA from Fe-NTA-treated and vehicle control animals was assayed by 32P-postlabeling. Thin-layer chromatography and quantitative analysis of two labeled nucleotide fractions of increasing polarity, L and C, showed that three spots (L1, L2, and C3) were intensified 3.5- to 4.2-fold in treated animals. L1 consisted of subfractions L1a, L1b, and L1c, which could be resolved chromatographically. L1c, L2, and C3 were identical to DNA oxidation products generated by the Fenton reaction in vitro, while L1a and L1b apparently did not arise by this mechanism. DNA damage and toxicity appeared reduced in younger animals and animals treated in the morning, presumably due to differences in antioxidant defenses. Liver and lung (non-target organs) DNA did not exhibit enhanced L1, L2, and C3 spots. In addition to augmenting renal I-compounds, Fe-NTA reduced the levels of three major polar kidney I-compounds (C4, C5, and C6) to 22-53% of control. This reduction did not appear to arise by direct oxidative DNA damage, resembling the previously documented loss of liver I-compounds induced by numerous hepatocarcinogens. Two of these I-compounds (C4 and C5) have been reported to exhibit positive linear correlations with median lifespan of male F344 rats. The pleiotropic response of kidney I-compound levels to Fe-NTA was consistent with different roles of different types (I and II) of I-compounds in Fe-NTA-mediated renal carcinogenesis. The results strongly support a causal relationship between oxidative DNA lesions and Fe-NTA-mediated carcinogenesis.
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PMID:Intensification and depletion of specific bulky renal DNA adducts (I-compounds) following exposure of male F344 rats to the renal carcinogen ferric nitrilotriacetate (Fe-NTA). 753 Dec 86

Effects of dietary probucol on renal damage induced by a renal carcinogen, ferric nitrilotriacetate (Fe-NTA), in male Wistar rats were quantitatively investigated with a computer-mediated image analyzer. The kidneys of rats fed a 1% probucol diet were protected from necrosis and lipid peroxidation induced by a single i.p. treatment with Fe-NTA solution at 5 mg Fe/kg body wt and were significantly resistant to a higher dose. For the parameter of lipid peroxidation, Schiff's staining method was utilized to demonstrate the extent of formation of aldehydes, products of lipid peroxidation. Thus following injection of Fe-NTA solution at 10 mg Fe/kg body wt the average areas of tubular necrosis were 85.8% versus 56.9% and the positive areas for Schiff's staining were 15.3% versus 5.6% in the renal cortices of rats fed control of 1% probucol diets respectively. These results indicate that probucol provides protection against Fe-NTA-induced nephrotoxicity through its antioxidant properties. In addition to being a cholesterol-lowering drug, useful for the control of hypercholesterolemia, probucol may therefore be beneficial for prevention and treatment of various pathogenic processes including those leading to carcinogenesis.
Carcinogenesis 1995 Oct
PMID:Inhibitory effect of probucol on nephrotoxicity induced by ferric nitrilotriacetate (Fe-NTA) in rats. 758 65

Ferric nitrilotriacetate (Fe-NTA) induces renal proximal tubular damage associated with lipid peroxidation and oxidative DNA base modifications that finally leads to a high incidence of renal adenocarcinoma in rodents. In the present study, we report on the in vivo formation of DNA-protein cross-links (DPCs) involving thymine and tyrosine in the renal chromatin of Wistar rats treated with single or repeated i.p. administration of Fe-NTA. Analyses of chromatin samples by gas chromatography/mass spectrometry revealed a significant increase in the amount of 3-[(1,3-dihydro-2,4-dioxopyrimidin-5-yl)-methyl]-L-tyrosine (Thy-Tyr cross-link) 24 and 48 hr after the administration of Fe-NTA. At 19th day of Fe-NTA treatment, the amount of Thy-Tyr cross-link decreased to the control level, indicating the presence of cellular repair activity. Thy-Tyr cross-link may play a role in the genetic alteration of this renal carcinogenesis model, since mitoses for regeneration of renal proximal tubules were closely associated with the increase in DPCs.
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PMID:Treatment of Wistar rats with a renal carcinogen, ferric nitrilotriacetate, causes DNA-protein cross-linking between thymine and tyrosine in their renal chromatin. 762 72

An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces proximal tubular necrosis, a consequence of lipid peroxidation, that finally leads to a high incidence of renal adenocarcinoma in rodents. Lipid peroxidation as monitored by formation of thiobarbituric acid-reactive substances and free 4-hydroxy-2-nonenal (HNE) was observed in the kidney homogenates of rats treated with Fe-NTA. Based on the fact that HNE is capable of reacting with cellular proteins, we attempted to detect the localization of HNE-modified proteins in rat kidney tissues with an immunohistochemical procedure. By means of an immunohistochemical technique using polyclonal antibody against the HNE-modified proteins, it was shown that HNE-modified proteins are formed in the target cells of this carcinogenesis model. HNE-modified proteins were detected in the renal proximal tubules 1 hr after i.p. administration of Fe-NTA (15 mg of iron per kg). Intense positivity was found in the cells with degeneration. After 6 hr, the level of HNE-protein conjugates decreased due to the subsequent necrosis. The intensity of the immunochemical reaction with HNE-modified proteins increased in parallel with an increase in the amounts of thiobartituric acid-reactive substances and free HNE that were found. Furthermore, histochemical detection of aldehydes by cold Schiff's reagent demonstrated that location of aldehydes was identical to that of the HNE-modified proteins determined by immunohistochemical procedures. It would thus appear that the production of HNE, a genotoxic and mutagenic aldehyde, and its reaction with proteins may play a role in Fe-NTA-induced renal carcinogenesis.
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PMID:Formation of 4-hydroxy-2-nonenal-modified proteins in the renal proximal tubules of rats treated with a renal carcinogen, ferric nitrilotriacetate. 814 63


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