Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, structural changes of the p53 gene in primary specimens of human colorectal carcinomas were analyzed by polymerase chain reaction mediated-DNA sequencing method. Point mutations of p53 gene, including an intronic mutation case, were detected in 8 of 14 carcinomas (57%). Point mutations of the gene were also observed in 2 of 2 adenomas, suggesting that mutations occur prior to the carcinoma stage. These results support that p53 gene plays an important role in the development of colorectal cancer. The frequency of Ki-ras oncogene mutations was also studied by polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP). This resulted in the rate of 42% (10/24), a quite similar value obtained by other methods. As PCR-SSCP analysis is a convenient method to detect point mutation, we have now examined 24 colorectal cancers for the p53 gene by this method, and detected the mutations. Furthermore, expression of the DCC gene, a candidate of tumor suppressor gene involved in colorectal carcinogenesis, was examined by reverse transcriptase-mediated PCR (RT-PCR) assay, resulting in significant reduction on the DCC expression in 8 of 14 carcinoma cases (57%).
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PMID:Mutations of the p53 gene and other genes involving in human colorectal carcinogenesis. 130 99

The neu oncogene has been demonstrated to be a potent transforming gene in rodent fibroblasts. The overexpression of the human erbB-2/neu oncogene has been implicated in the development and/or prognosis of several human carcinomas including that of the prostate. To assess the transforming potential of the activated rat neu oncogene in prostatic epithelial carcinogenesis, this laboratory has transfected a cloned non-tumorigenic, rat ventral prostate epithelial cell line, NbE-1.4, with an activated, point-mutated neu oncogene. Transfection of NbE-1.4 cells with the activated neu oncogene expression vector, pSV-neu-T (neu-T), resulted in an altered cell morphology, an increase in soft agar colony-forming efficiency, and conversion to a tumorigenic phenotype. Although the parental NbE-1.4 cells expressed endogenous c-neu mRNA, a reverse transcriptase polymerase chain reaction assay determined that the neu-T-transfected clones expressed only the point-mutated neu-T mRNA. The suppression of the c-neu transcripts occurred regardless of the neu-T mRNA level expressed in these cell clones. These data provide evidence to show that low-level expression of an activated neu oncogene alone was insufficient to transform rat prostate epithelial cells. Rather, overexpression of an activated neu oncogene correlated well with the acquisition of a tumorigenic phenotype by the NbE-1.4 epithelial cell line.
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PMID:Acquisition of a tumorigenic phenotype by a rat ventral prostate epithelial cell line expressing a transfected activated neu oncogene. 135 May 10

Human papillomaviruses (HPV) are associated with papillomatosis of the larynx, trachea, and bronchi in decreasing order of frequency, and these papillomatosis lesions may become malignant. When the patients are not selected for a history of papillomatosis, the frequency of HPV in bronchogenic carcinoma tissue is 1-5%. In order to develop a model for investigating the role of HPV in human bronchogenic carcinogenesis, normal human bronchial epithelial cells were transfected with cloned full-length HPV16 or HPV18. Two HPV18-transformed cell lines (BEP1 and BEP2) and one HPV16-transformed cell line (BEP3) were established. These nontumorigenic epithelial cell lines have: (a) attained over 100 population doublings in vitro; (b) mutually exclusive human marker chromosomes; (c) HPV DNA in forms that are consistent with chromosomal integration by Southern analysis; (d) HPV E6, E7, and E6* mRNA transcripts by Northern and reverse transcriptase-polymerase chain reaction analysis; and (e) diminished confluence-induced squamous differentiation. These cell lines should be useful for studying mechanisms involved in proliferation, differentiation, and neoplastic transformation of human bronchial epithelial cells.
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PMID:Immortalization of normal human bronchial epithelial cells by human papillomaviruses 16 or 18. 171 49

The action of DNA polymerase (Sequenase Version 2.0) on an oligonucleotide template containing a 7-bromomethyl-benz[a]anthracene-deoxyadenosine adduct flanked by thymidine residues was investigated. The polymerase incorporated deoxyadenosine or deoxyguanosine residues opposite the thymidine 3' to the adduct with similar efficiencies. Whereas the normal A.T base pair led to arrest of polymerase progression along the template, formation of the G.T mismatch allowed incorporation of thymidine opposite the adduct and further primer extension. This mispair-mediated bypass was also seen with AMV reverse transcriptase and may represent a novel mechanism for overcoming the replication block of a bulky carcinogen--DNA adduct.
Carcinogenesis 1991 Nov
PMID:Bypass of a hydrocarbon adduct in an oligonucleotide template mediated by mispairing adjacent to the adduct. 171 21

To gain insight into the mechanisms by which mutations are induced in human cells by carcinogens, we have determined the kinds and location (spectrum) of mutations induced in the coding region of the hypoxanthine (guanine) phosphoribosyltransferase (HPRT) gene by (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE). Individual populations of diploid human fibroblasts were treated with BPDE, or were left untreated (control). After a suitable expression period, the progeny cells were selected for resistance to 6-thioguanine. Individual drug-resistant colonies were isolated, and the mRNA in the lysate of 100-400 cells from each colony was copied directly into cDNA using reverse transcriptase. The cDNA of the HPRT gene of 29 unequivocally independent mutants from BPDE-treated populations and 13 from the control populations was amplified 10(11)-fold, and the product was sequenced directly. Twenty-three of the 29 BPDE-induced mutants examined contained a single base pair substitution; four exhibited two base pair substitutions. Eight out of 13 control mutants exhibited base pair substitutions, and four others were missing a complete exon. Thirty of the 32 base pair substitutions in the BPDE-induced mutants involved G.C base pairs, primarily G.C----T.A transversions. The majority (89%) of the base pair substitutions observed in the mutants from the control population involved an A.T base pair. Base substitutions were found throughout the coding region of the gene, but 41% of those seen in mutants from the BPDE-treated population and 44% of those from the untreated population were located in the first half of exon 3.
Carcinogenesis 1991 Jan
PMID:Kinds and location of mutations induced by (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene in the coding region of the hypoxanthine (guanine) phosphoribosyltransferase gene in diploid human fibroblasts. 189 56

N2,3-Ethenoguanine (epsilon G) is a product of vinyl chloride reaction with DNA in vivo and of its ultimate metabolite, chloroacetaldehyde, in vitro. The synthesis of the very labile 5'-triphosphate of N2,3-etheno-deoxyguanosine (epsilon dGuo) has made it possible to study the base pairing properties of this derivative placed opposite a defined normal base in a 25-base oligonucleotide template. The kinetic parameters, Km and Vmax were determined from elongation of a [32P]5'-end labeled primer annealed one base prior to the designated template base, epsilon G.T pairs, which would be mutagenic, were formed with a frequency 2- to 4-fold greater than the analogous wobble pair, G.T. The non-mutagenic pairing, epsilon G.C, occurs with a lower frequency than G.C but neither epsilon G.T or epsilon G.C constitute a significant block to replication. The frequency of epsilon G.T formation was similar with all polymerases tested: Escherichia coli DNA polymerase I (Klenow fragment), exonuclease-free Klenow, Drosophila melanogaster polymerase alpha-primase complex and human immunodeficient virus-I reverse transcriptase (HIV-RT). It is concluded that these prokaryotic and eukaryotic replicating enzymes apparently recognize the same structural features, and on replication G----A transitions would occur, which in turn, could initiate malignant transformation. In contrast to the G.T mismatch which is known to have a specific repair system, etheno derivatives are apparently not repaired in vivo.
Carcinogenesis 1991 Apr
PMID:Evidence for the mutagenic potential of the vinyl chloride induced adduct, N2, 3-etheno-deoxyguanosine, using a site-directed kinetic assay. 201 38

Two alkylation products implicated in initiation of carcinogenesis are O6-alkylguanine (m6G) and O4-alkylthymine (m4T). We have used site-specific insertion of these derivatives into oligonucleotides and measured the kinetic constants of various pairings, using both prokaryotic and eukaryotic polymerases for replication. Preliminary data are also reported for another carcinogen product, N2,3-ethenodeoxyguanosine ( epsilon G). The immediate neighbor bases play an important role in determining the frequency of specific changed basepairing and subsequent elongation of the annealed primer. However, both m4T and m6G prefer to form a type of G.T pairing which would lead to the transitions: G.C----A.T or T.A----C.G. The enzymes were the Klenow fragment of E. coli DNA polymerase I (Kf), engineered 3'----5' exonuclease-free Kf (exo-free Kf), polymerase alpha-primase complex from Drosophila melanogaster or calf thymus, and human immunodeficient virus-I reverse transcriptase (HIV-I RT). All enzymes led to approximately the same frequency of transitions. It is postulated that the mutation frequency at a given site is primarily a function of the structure of the sequence around the target site.
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PMID:Site-directed mutagenesis for quantitation of base-base interactions at defined sites. 223 12

N2,3-Ethenoguanine (N2,3-epsilon G) was recently identified in the liver of vinyl chloride-exposed rats. We have now synthesized the nucleoside and the 5'-diphosphate which was copolymerized with CDP. The deoxypolynucleotide complement, synthesized by AMV reverse transcriptase contained, in addition to dG, dC and dT. The total pyrimidine content was approximately equivalent to the N2,3-epsilon G content of the template. Incorporation of dC is neither lethal nor mutagenic, while dT incorporation represents a mutagenic event, occurring with approximately 20% frequency. N2,3-epsilon G X dT base pairs can have two hydrogen bonds with minimal helical distortion, as is also the case for N2,3-epsilon G X C base pairs. N2,3-epsilon G is the only derivative formed in vivo by the human carcinogen, vinyl chloride, that can be shown to have a high probability of causing transitions which could initiate malignant transformation.
Carcinogenesis 1987 May
PMID:The vinyl chloride-derived nucleoside, N2,3-ethenoguanosine, is a highly efficient mutagen in transcription. 358 34

Endogenous avian RNA tumor virus gene expression was induced in chick embryo cells by the 1,1,1-trichloro-2-, 2-bis(p-chlorophenyl ethane) metabolites bis(chlorophenyl)acetic acid and dichlorodiphenyl dichloroethylene and the antibacterial agent hexachlorophene. Line 100 x 7, C/ABE, chick cell cultures were incubated with each of these chemicals or the known endogenous virus inducer bromodeoxyuridine. At subtoxic levels, all four chemicals induced the production of virus particles as determined by assay for the viral-specific reverse transcriptase and infectivity. Since the endogenous virus produced is of subgroup E and consequently unable to infect surrounding cells of the type C/ABE, amplification of the induced virions was accomplished by infecting the subgroup E susceptible cell line 15B C/C with supernatants from the chemically treated cultures. Fluorescent antibody treatment of line 100 x 7 C/ABE cultures showed approximately 35% to 40% of the cells stained in the chemically treated cell cultures, suggesting that only a portion of the cells were responding to the chemical induction.
Carcinogenesis 1981
PMID:Induction of endogenous viral gene expression by halogenated hydrocarbons. 616 9

The action of 12-O-tetradecanoylphorbol-13-acetate (TPA) on several retrovirus-related functions was investigated in four virus-host cell systems. The following effects were recorded: (i) in STU-mice, infected with the Friend virus complex (Friend) murine leukaemia virus/Friend spleen focus forming virus) and treated with TPA (50 ng/g) for one week prior to infection, the number of spleen foci increased 5-fold over the control. (ii) Addition of TPA (0.04 to 40 ng/ml) to virus-producing cell systems resulted in a 2-fold increase of extracellular reverse transcriptase activity. The maximum response was observed in Friend leukemia virus-producing mouse cells at 0.1 to 0.4 ng TPA/ml and in simian sarcoma virus-producing rat cells at 4 ng/ml. (iii) The efficiency of transformation of BalbC 3T3 cells by Moloney murine sarcoma virus, tested in a focus formation assay, was slightly enhanced by TPA. (iv) TPA inhibited the induction of endogenous virus formation in B cell mitogen-stimulated spleen cell cultures from BalbC mice.
Carcinogenesis 1982
PMID:Diverse effects: augmentation, inhibition, and non-efficacy of 12-O-tetradecanoylphorbol-13-acetate (TPA) on retrovirus genome expression in vivo and in vitro. 617 39


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