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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study assessed the effect of lead acetate (Pb) on N-(4'-fluoro-4-biphenyl)acetamide (FBPA)-induced renal carcinogenesis. A quantitative investigation was performed to determine the effects of Pb on the numerical density (Nv) and percent volume (%V) of FBPA-induced renal tubular hyperplasia and microscopic nodules. A secondary goal was to evaluate, on a quantitative basis, the role of these putative premalignant lesions in the development of renal carcinoma. Additionally, by quantifying the number per unit area of karyomegalic cells, their relationship to the neoplastic process was examined. Generally, Pb was found to accelerate the onset and development of all renal lesions. Karyocytomegaly did not serve as an indicator of the degree of carcinogenicity of any of the treatment regimens.
Carcinogenesis 1984 Sep
PMID:Effect of lead acetate on N-(4'-fluoro-4-biphenyl)acetamide-induced renal carcinogenesis in the rat. 646 1

A population-based case-control study of renal cell carcinoma (495 cases and 697 controls) in the Minneapolis-St. Paul seven-county metropolitan area implicated cigarette smoking as a risk factor with an odds ratio (OR) among men of 1.6 (95% confidence intervals: 1.1-2.4) and among women of 1.9 (1.3-3.0). A statistically significant dose response was observed in both sexes for pack-years of cigarette use. On the basis of calculations of attributable risk, it was estimated that 30% of renal cell cancers among men and 24% among women were due to smoking. High relative adult weight as measured by the body mass index (BMI) was found to be a major risk factor among women but not among men, with those in the highest 5% of the BMI having an OR of 5.9 (1.8-20.4) in comparison to the lowest quartile. This association with excess weight was not seen at age 20, but it became more pronounced with increasing age, suggesting that the primary influence of weight gain is during the late stages of renal carcinogenesis. Excess risks were also related to ethnic background (particularly, German), which may account in part for the elevated incidence of renal cancer in the North Central area of the United States. In addition, positive associations were observed for long-term use of phenacetin-containing analgesics, heavy meat consumption, and heavy tea drinking (females only). An occupational clue was provided by an increased risk for exposure to petroleum, tar, and pitch products. Excesses of certain urologic and cardiovascular diseases were also observed among the cases compared to controls.
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PMID:A population--based case--control study of renal cell carcinoma. 658 15

The effects of a single injection of streptozotocin, at a dosage of 50 mg/kg body weight, have been studied in female inbred WAG rats. The resultant diabetes in the streptozotocin treated animals was treated in one group of animals by an intraportal pancreatic islet cell transplantation whilst another group received no transplant or insulin treatment. The incidence of tumours were determined at autopsy in animals sacrificed at regular intervals. Tumours, apart from one renal adenocarcinoma, were seen only in the liver and only in streptozotocin treated animals. Liver nodules and cysts were most common in animals which had received both streptozotocin and an islet cell transplant.
Carcinogenesis 1981
PMID:Liver tumours following streptozotocin administration in rats and the effects of pancreatic islet cell transplantation. 679 61

The ability of vitamin C to inhibit induction of renal carcinoma by estrogens was tested in male Syrian hamsters in vivo. The animals received estrogen (estradiol or diethylstilbestrol) implants s.c. Hamsters which were continuously given vitamin C, administered in the drinking water for estradiol-treated or in the food for diethylstilbestrol-treated animals, were observed to develop renal carcinoma with a significantly lower incidence (10 of 33 animals with estradiol implants; 14 of 29 animals with diethylstilbestrol implants) than animals which did not receive vitamin C supplementation (16 of 23 animals with estradiol implants; 11 of 13 animals with diethystilbestrol implants). Administration of vitamin C to estradiol-treated hamsters for only the first 3 months of the carcinogenesis experiment had no effect on tumor incidence, but vitamin C in drinking water for the last 3 months also lowered incidence. Vitamin C supplementation did not significantly alter the absorption of estrogen from the implant; it did not change the estrogenic effect on the hamsters nor did it significantly influence estrogen-dependent H-301 tumor cell growth. The results were taken as evidence for a mechanism of tumor induction via oxidation of estrogens to reactive metabolites capable of inducing kidney tumors.
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PMID:Inhibition of estrogen-induced renal carcinoma in Syrian hamsters by vitamin C. 688 21

Enhanced cell proliferation occurs at several stages of renal tumorigenesis. Initiation by genotoxic nephrocarcinogens such as dimethylnitrosamine (DMN) is likely a result of DNA damage coupled with an initial burst of DNA synthesis associated with the cytotoxic effects of the compound. The level of initiation by DMN can be further enhanced by unilateral nephrectomy or hydronephrosis, which induces a brief burst of cell proliferation followed by tumorigenesis in the contralateral kidney. The role of sustained cell proliferation in renal tumor development is less well understood. The most compelling evidence comes from studies with nongenotoxic renal carcinogens such as unleaded gasoline and d-limonene, which induce alpha 2u-globulin (alpha G) nephropathy and renal epithelial tumors exclusively in male rats. Sustained increases in cell proliferation in these studies depend on the presence of a chemical-alpha G complex in phagolysosomes of P2 proximal tubule cells, which results in cytotoxicity and compensatory hyperplasia only in male F344 rats, but not female F344 rats or alpha G deficient male NBR rats. Furthermore, initiation-promotion experiments demonstrated a strong correlation between the dose-response of cell proliferation and the incidence of preneoplastic and neoplastic lesions. Clearly, similar correlative studies with a number of other renal carcinogens and non-carcinogens are warranted before general conclusions can be made. Cell proliferation is excessively elevated in tubules affected by chronic progressive nephropathy, but the significance of the lesion to renal carcinogenesis is unclear. Elucidating mechanisms of renal cell proliferation are necessary for our understanding of cause and effect relationships. An exciting recent finding is altered expression of transforming growth factor-alpha in hereditary rat renal cell carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cell proliferation and renal carcinogenesis. 751 72

The Eker rat hereditary renal carcinoma is an excellent example of a Mendelian dominant predisposition to a specific cancer in an experimental animal. We recently reported that a germline insertion in the rat homologue of the human tuberous sclerosis (TSC2) gene gives rise to the dominantly inherited cancer in the Eker rat model. The function of the TSC2/Tsc2 gene product (called "tuberine" in the human case) is not yet understood, although it contains a short amino acid sequence homologous to the ras family GTPase-activating proteins (GAP3). In the study, we isolated subtracted cDNA clones having increased expression in Eker renal carcinoma cells, using a modified representational difference analysis method to search for additional genes specifically involved in renal carcinogenesis. Here we identified four genes: the third component of the complement (C3) gene, the fos-related antigen I (fra-1) gene, an unknown gene (designated as being expressed in renal carcinoma: erc) and the calpactine I heavy-chain (Annexin II) gene.
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PMID:Renal carcinogenesis in the Eker rat. 755 44

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

The purpose of our study was to detect somatic changes in renal cell carcinoma by multilocus fingerprinting. DNA fingerprints were generated from the DNA of normal and malignant renal tissue samples of 29 patients with nonhereditary kidney carcinoma by using oligonucleotide probes specific for simple repeat motifs such as (GTG)5, (CA)8, (GACA)4, or (TTAGGG)3. Each probe rendered a typical fingerprint pattern, because it is specific with respect to the target regions recognized in the genome. The restriction enzymes used were HinfI and HaeIII. Changed banding patterns were detected by using (GTG)5 in 20% of the tumors, in 20% for (CA)8 after HinfI digestion, and in 10% after HaeIII digestion. Even more informative probes were (GACA)4, showing 70% changes after HaeIII digestion, and (TTAGGG)3, with 80% changes after digestion with either enzyme. Since the simple repeat motifs recognized by (GACA)4 are localized on the short arms of the acrocentric chromosomes (13, 14, 15, 21, and 22), it is possible that sequences important for renal carcinogenesis are present in these regions. The observation of changes in regions to which (TTAGGG)3 hybridizes points to an involvement of DNA elements in telomeric sequence related regions in human kidney tumor formation.
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PMID:Detection of somatic changes in human renal cell carcinomas with oligonucleotide probes specific for simple repeat motifs. 766 46

Tumor suppressor genes have been found to have loss of function in a number of malignancies. This loss of function is believed to contribute to malignant transformation or metastatic spread. In the present study, expression of the retinoblastoma (RB) tumor suppressor gene was examined in cell lines and tumor tissue obtained from primary renal and metastatic sites in patients with metastatic renal cell carcinoma. Three of fifteen (20%) of informative renal carcinoma cell lines had loss of heterozygosity (LOH) in the RB gene (intron 20) detected by polymerase chain reaction analysis. Using restriction fragment length polymorphism (RFLP) analysis, 7 of 22 (32%) informative cell lines had LOH centromeric to the RB gene at the D13S1 locus. No LOH (0 of 7) was seen telomeric to the RB gene at the D13S2 locus. None of the 28 cell lines examined had decreased RB mRNA expression compared with short-term cultures of proximal renal tubular cells. Western blotting demonstrated phosphorylated and unphosphorylated forms of RB protein of expected molecular weight in all 41 cell lines (33 primary and 8 metastatic) examined. Twenty-nine primary cell lines and 6 metastatic cell lines all demonstrated normal immunohistochemical staining. Loss of RB immunohistochemical staining in paraffin-embedded tissue was detected in none of the primary tumors (0 of 30) or metastatic tumors (0 of 12). The absence of abnormalities of RB expression detected in these renal cell carcinomas suggests that abnormalities of the RB gene are not central to malignant transformation or progression in this tumor type; however, another tumor suppressor gene centromeric to the RB locus may be important in renal cell carcinogenesis.
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PMID:Loss of heterozygosity occurs centromeric to RB without associated abnormalities in the retinoblastoma gene in tumors from patients with metastatic renal cell carcinoma. 775 92

It has been speculated that renal cell carcinoma (RCC) is an example of a double-loss mutation. We analyzed the age distribution of 71 cases of familial RCC and of 11 population-based cancer registries [German Democratic Republic, Denmark, Finland, Norway, Sweden, U.S.A. Whites, U.S.A. Blacks, Miyagi and Osaka Prefectures (Japan), Hong Kong, and Israeli Jews] according to the multi-hit and clonal growth models of carcinogenesis. The analysis rules out a double-loss mechanism for RCC. On both of the two models analyzed, carcinogenesis in the familial cases of RCC arises as a result of a three- to ten-fold increase in the average rate of mutation at the susceptible loci, as compared with the sporadic cases. In general, the clonal growth model provides a somewhat better fit to the age-distribution of RCC incidence than does the multi-hit model.
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PMID:Familial and sporadic human renal cell carcinoma: evidence against a double-loss mechanism of carcinogenesis. 776 7


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