Low incidence of point mutations in H-, K- and N-ras oncogenes and p53 tumor suppressor gene in renal cell carcinoma and peritoneal mesothelioma of Wistar rats induced by ferric nitrilotriacetate. 1995

Y Nishiyama, and H Suwa, and K Okamoto, and M Fukumoto, and H Hiai, and S Toyokuni
Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University.

An iron chelate, ferric nitrilotriacetate (Fe-NTA, induces renal proximal tubular damage, a consequence of iron-catalyzed free radical reactions, that finally leads to a high incidence of renal cell carcinoma (RCC) in rodents. Previous studies have identified, within 24 h after administration of Fe-NTA, lipid peroxidation products, aldehyde-modified proteins and a variety of modified DNA bases such as 8-hydroxyguanine that may be mutagenic in vivo. In the present study, pathological features of the RCCs were studied, and, in an effort to correlate them with carcinogen-specific molecular events in Fe-NTA-induced carcinogenesis, the H-, K- and N-ras oncogenes and the p53 tumor suppressor gene were investigated for the presence of mutations. Fe-NTA-induced RCCs showed similarity to human RCCs in that they are often invasive, metastatic and fatal. None (0 of 12) of the tumors had mutation in codons 12, 13 and 61 of the H-, K- and N-ras genes by direct sequencing. Only one (1 of 12) tumor with high grade histology revealed a CGC-to-CTC (Arg to Leu) transversion in codon 246 of the p53 gene by the use of single strand conformation polymorphism (SSCP) analysis and direct sequencing. High expression of mutant p53 protein was confirmed by Western blotting and immunohistochemistry. Study of three peritoneal mesotheliomas induced by Fe-NTA revealed no mutation in ras and p53 genes. These results suggest that the ras and p53 genes are not the major targets of mutation in Fe-NTA-induced carcinogenesis of kidney and mesothelium. Instead, p53 mutation may work for potentiation of malignant character in Fe-NTA-induced renal carcinogenesis.

UI MeSH Term Description Entries
D007680 Kidney Neoplasms Tumors or cancers of the KIDNEY. Cancer of Kidney,Kidney Cancer,Renal Cancer,Cancer of the Kidney,Neoplasms, Kidney,Renal Neoplasms,Cancer, Kidney,Cancer, Renal,Cancers, Kidney,Cancers, Renal,Kidney Cancers,Kidney Neoplasm,Neoplasm, Kidney,Neoplasm, Renal,Neoplasms, Renal,Renal Cancers,Renal Neoplasm
D008297 Male Males
D008654 Mesothelioma A tumor derived from mesothelial tissue (peritoneum, pleura, pericardium). It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos. (Dorland, 27th ed) Mesotheliomas
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009571 Nitrilotriacetic Acid A derivative of acetic acid, N(CH2COOH)3. It is a complexing (sequestering) agent that forms stable complexes with Zn2+. (From Miall's Dictionary of Chemistry, 5th ed.) Aluminum Nitrilotriacetate,Dysprosium Nitrilotriacetate,Trisodium Nitrilotriacetate,Acid, Nitrilotriacetic,Nitrilotriacetate, Aluminum,Nitrilotriacetate, Dysprosium,Nitrilotriacetate, Trisodium
D010534 Peritoneal Neoplasms Tumors or cancer of the PERITONEUM. Peritoneal Carcinomatosis,Peritoneal Surface Malignancy,Carcinomatosis, Peritoneal,Malignancy, Peritoneal Surface,Neoplasm, Peritoneal,Peritoneal Carcinomatoses,Peritoneal Neoplasm,Peritoneal Surface Malignancies,Surface Malignancy, Peritoneal
D011905 Genes, ras Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein. Ha-ras Genes,Ki-ras Genes,N-ras Genes,c-Ha-ras Genes,c-Ki-ras Genes,c-N-ras Genes,ras Genes,v-Ha-ras Genes,v-Ki-ras Genes,H-ras Genes,H-ras Oncogenes,Ha-ras Oncogenes,K-ras Genes,K-ras Oncogenes,Ki-ras Oncogenes,N-ras Oncogenes,c-H-ras Genes,c-H-ras Proto-Oncogenes,c-Ha-ras Proto-Oncogenes,c-K-ras Genes,c-K-ras Proto-Oncogenes,c-Ki-ras Proto-Oncogenes,c-N-ras Proto-Oncogenes,ras Oncogene,v-H-ras Genes,v-H-ras Oncogenes,v-Ha-ras Oncogenes,v-K-ras Genes,v-K-ras Oncogenes,v-Ki-ras Oncogenes,Gene, Ha-ras,Gene, Ki-ras,Gene, v-Ha-ras,Gene, v-Ki-ras,Genes, Ha-ras,Genes, Ki-ras,Genes, N-ras,Genes, v-Ha-ras,Genes, v-Ki-ras,H ras Genes,H ras Oncogenes,H-ras Gene,H-ras Oncogene,Ha ras Genes,Ha ras Oncogenes,Ha-ras Gene,Ha-ras Oncogene,K ras Genes,K ras Oncogenes,K-ras Gene,K-ras Oncogene,Ki ras Genes,Ki ras Oncogenes,Ki-ras Gene,Ki-ras Oncogene,N ras Genes,N ras Oncogenes,N-ras Gene,N-ras Oncogene,c H ras Genes,c H ras Proto Oncogenes,c Ha ras Genes,c Ha ras Proto Oncogenes,c K ras Genes,c K ras Proto Oncogenes,c Ki ras Genes,c Ki ras Proto Oncogenes,c N ras Genes,c N ras Proto Oncogenes,c-H-ras Gene,c-H-ras Proto-Oncogene,c-Ha-ras Gene,c-Ha-ras Proto-Oncogene,c-K-ras Gene,c-K-ras Proto-Oncogene,c-Ki-ras Gene,c-Ki-ras Proto-Oncogene,c-N-ras Gene,c-N-ras Proto-Oncogene,ras Gene,ras Oncogenes,v H ras Genes,v H ras Oncogenes,v Ha ras Genes,v Ha ras Oncogenes,v K ras Genes,v K ras Oncogenes,v Ki ras Genes,v Ki ras Oncogenes,v-H-ras Gene,v-H-ras Oncogene,v-Ha-ras Gene,v-Ha-ras Oncogene,v-K-ras Gene,v-K-ras Oncogene,v-Ki-ras Gene,v-Ki-ras Oncogene
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D002292 Carcinoma, Renal Cell A heterogeneous group of sporadic or hereditary carcinoma derived from cells of the KIDNEYS. There are several subtypes including the clear cells, the papillary, the chromophobe, the collecting duct, the spindle cells (sarcomatoid), or mixed cell-type carcinoma. Adenocarcinoma, Renal Cell,Carcinoma, Hypernephroid,Grawitz Tumor,Hypernephroma,Renal Carcinoma,Adenocarcinoma Of Kidney,Adenocarcinoma, Renal,Chromophil Renal Cell Carcinoma,Chromophobe Renal Cell Carcinoma,Clear Cell Renal Carcinoma,Clear Cell Renal Cell Carcinoma,Collecting Duct Carcinoma,Collecting Duct Carcinoma (Kidney),Collecting Duct Carcinoma of the Kidney,Nephroid Carcinoma,Papillary Renal Cell Carcinoma,Renal Cell Cancer,Renal Cell Carcinoma,Renal Cell Carcinoma, Papillary,Renal Collecting Duct Carcinoma,Sarcomatoid Renal Cell Carcinoma,Adenocarcinoma Of Kidneys,Adenocarcinomas, Renal Cell,Cancer, Renal Cell,Carcinoma, Collecting Duct,Carcinoma, Collecting Duct (Kidney),Carcinoma, Nephroid,Carcinoma, Renal,Carcinomas, Collecting Duct,Carcinomas, Collecting Duct (Kidney),Carcinomas, Renal Cell,Collecting Duct Carcinomas,Collecting Duct Carcinomas (Kidney),Hypernephroid Carcinoma,Hypernephroid Carcinomas,Hypernephromas,Kidney, Adenocarcinoma Of,Nephroid Carcinomas,Renal Adenocarcinoma,Renal Adenocarcinomas,Renal Carcinomas,Renal Cell Adenocarcinoma,Renal Cell Adenocarcinomas,Renal Cell Cancers,Renal Cell Carcinomas,Tumor, Grawitz
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries

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