Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of 2-chloroacetaldehyde, CAA, a metabolite of vinyl chloride and 2-chloroacetal, CAC, an ethyl diester of chloroacetaldehyde, on DNA synthesis in animal cells has been investigated. Both compounds drastically inhibited DNA synthesis at 10 to 20 microM. The inhibitory effect of the chemicals appears to be directly on DNA synthesis rather than on the uptake of thymidine or the formation of nucleotides. Residual DNA made in the presence of CAA had an average chain length of 300 nucleotides compared to a length of several thousand nucleotides in the absence of CAA. Synchronization experiments revealed that the inhibitory effect is reversible if 2-chloroacetaldehyde is removed within two hours but not after longer exposures.
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PMID:2-Chloroacetaldehyde and 2-chloroacetal are potent inhibitors of DNA synthesis in animal cells. 232 35

Vinyl chloride is a potent hepatocarcinogen which reacts with DNA to generate etheno bases. In order to determine whether mutational patterns in target genes in vivo are characteristic of vinyl chloride and could be explained by the mutagenic properties of the etheno bases, human and rat liver tumours associated with exposure to vinyl chloride were analysed for point mutations in the ras and p53 genes. In this paper, we review these data and report our latest results on animal tumours. Two alterations were found which could be attributed to a direct effect of vinyl chloride: a GC-->AT transition which leads to a GGC-->GAC mutation at codon 13 of the Ki-ras gene in human liver angiosarcomas, and lesions at AT base pairs, mostly AT-->TA transversions, which lead to mutations in the p53 gene in human and rat angiosarcomas and to a CAA-->CTA mutation at codon 61 of the Ha-ras gene in rat hepatocellular carcinomas.
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PMID:Vinyl chloride-specific mutations in humans and animals. 1062 31

Previous studies have shown that a high proportion (5/6) of human liver angiosarcomas (ASL) associated with exposure to vinyl chloride (VC) contains a GC-->AT mutation at the Ki-ras codon 13. This mutation, however, has not been found in 5 ASL or 2 hepatocellular carcinomas (HCC) induced in rats by VC. These 2 HCC did contain a mutation at codon 61 of the Ha-ras gene. In order to extend this study and further explore the mechanisms of tumour induction, an additional 6 ASL and 6 HCC induced in rats by VC were analysed for ras gene point mutations, as well as 10 rat and 10 murine ASL induced by vinyl fluoride (VF), and 5 ASL, 6 Kupffer cell sarcomas, 4 HCC and 2 cholangiocellular carcinomas induced by Thorotrast in rats. Tumour DNA was analysed by PCR-SSCP and direct sequencing. None of the rodent ASL contained a mutation at codon 13 of the Ki-ras gene showing that the ras gene mutational pattern is species-specific. The CAA-->CTA mutation, previously found at codon 61 of the Ha-ras gene in rat HCC, was observed in 5 further VC-induced HCC but was not detected in the Thorotrast-induced HCC, suggesting carcinogen-specificity. This mutation was also absent in VC-induced ASL, which supports the cell-specificity of the ras mutational pattern in chemically induced tumours. No predominant mutation was detected in VF- and Thorotrast-induced tumours. Thus, a given mutation in a tumour may be carcinogen-specific but also depend on the species and the cell type.
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PMID:Ras gene mutations in vinyl chloride-induced liver tumours are carcinogen-specific but vary with cell type and species. 1062 81

To study the genotoxic properties of 1,N6-ethenodeoxyadenosine (epsilondA) in human cells, a novel site-specific mutagenesis approach was developed, in which a single DNA adduct was uniquely placed in either strand of a shuttle plasmid vector. The analysis of progeny plasmid derived from the modified strand shows that epsilondA, when incorporated into the position of the second A of 5'-CAA (codon 61 of the ras gene), is mutagenic in human cells, inducing A-->T, A-->G, and A-->C mutations. The efficient induction of A-->T transversions in experiments using modified double- and singlestranded DNA substrates supports the hypothesis that A:T-->T:A transversions in human and animal tumors induced by vinyl compounds reflect misinsertion of dAMP opposite this adduct. Mutagenic events were similar when the adduct was incorporated into either the leading or the lagging strand. EpsilondA was more mutagenic than 8-oxodeoxyguanosine, which induced targeted G-->T transversions in HeLa cells. In Escherichia coli, epsilondA did not significantly miscode (<0.27%) even in the presence of induced SOS functions.
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PMID:Mutagenesis induced by a single 1,N6-ethenodeoxyadenosine adduct in human cells. 1094 16

DNA analysis of a newborn baby wrapped and kept in a vinyl bag for 15 years was performed. DNA isolated from the femur and humerus was used to determine the sex and kinship between the infant and the putative parents. Amplification of mtDNA, ABO, HLA, CST3, CST5, VWA, D12S66, D21S11, CSF1PO, TPOX, THO1 and 10Y polymorphisms and the amelogenin gene was carried out. Several mtDNA types were obtained, suggesting that the sample was contaminated by exogenous DNAs. One of the DNA samples obtained from the femur showed an identical mtDNA sequence to that of the mother except for one site, and this pattern was also found in another DNA sample. None of our laboratory personnel had that type, so we thought it was possible that this sample contained the target DNA. However, maternity was denied by the CST3 polymorphism. Finally, we concluded that the sample had been contaminated with exogenous DNA before we started to examine the body. Although it is difficult to determine the sources of this contamination, PCR amplification from highly degraded DNA is very sensitive to such contamination, and we must be even more careful in DNA analysis of such samples than in that of not so severely degraded specimens.
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PMID:DNA analysis of neonatal human remains wrapped and kept in a vinyl bag for 15 years. 1293 84