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)

Ha-ras activation in forestomach squamous cell carcinomas of CDF1 mice induced by 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), one of the heterocyclic amines isolated from broiled sardine was analyzed. Mutations were detected in two of three primary original carcinomas and two of four cell lines derived from other independent carcinomas by the polymerase chain reaction followed by analysis of single strand conformation polymorphism and direct sequencing. All the mutations detected were G----T transversions at the second letter of codon 13 resulting in an amino acid change from Gly to Val. This finding together with the previous reports on squamous cell carcinomas of the rat Zymbal gland suggest that MeIQ induces a specific type of mutation at a specific site of the Ha-ras gene during squamous cell carcinogenesis, in a species-independent manner.
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PMID:Detection of a Ha-ras point mutation by polymerase chain reaction-single strand conformation polymorphism analysis in 2-amino-3,4-dimethylimidazo[4,5-f]quinoline-induced mouse forestomach tumors. 154 Sep 38

3-Methyladenine DNA glycosylase II (Gly II), purified from Escherichia coli cells which carry the plasmid PYN1000, has been tested for its ability to release N2,3-ethanoguanine from DNA modified by the antitumor agent N-[2-chloroethyl-1,2-14C]-N'-cyclohexyl-N-nitrosourea ([14C]CCNU). Gly II has been shown to release N2,3-ethanoguanine in a protein- and time-dependent manner at a rate that exceeds the rate at which this enzyme releases other alkylated bases from [14C]CCNU-modified DNA. This finding widens the known substrate specificity for Gly II to include a modified base which bears an exocyclic ring structure, a class of modifications caused by a variety of chemical carcinogens.
Carcinogenesis 1991 Oct
PMID:Release of N2,3-ethanoguanine from haloethylnitrosourea-treated DNA by Escherichia coli 3-methyladenine DNA glycosylase II. 193 81

The peptide pyroGlu-Gln-Gly-Ser-Asn, recently isolated from mouse liver, inhibited DNA synthesis and proliferation in vitro of MH1C1 cells, a rat clonal strain derived from a Morris transplantable hepatoma. Both the biological peptide isolated from mouse liver and the synthetic homolog showed bell-shaped dose-response curves. Maximal inhibition (approximately 50%) was observed at two separate dose ranges: one at 10(-7)-10(-10) M, and one at 10(-14)-10(-15) M.
Carcinogenesis 1991 Feb
PMID:The peptide pyroGlu-Gln-Gly-Ser-Asn, isolated from mouse liver, inhibits growth of rat hepatoma cells in vitro. 199 86

Qualitative changes of glycoconjugates in luminal surface and goblet cell mucin from colon mucosa of 1,2-dimethylhydrazine (DMH)-treated rats were studied. Eight fluoresceinated lectins were used: Dolichos biflorus (DBA), Glycine max (SBA), Triticum vulgare (WGA), Limax flavus (LFA), Arachis hypogaea (PNA), Griffonia simplicifolia-I (GS-I), Ulex europaeus-I (UEA-I) and Canavalia ensiformis (Con A). The lectin-binding patterns were studied in tumors arising in proximal and distal portions of the colon, in transitional mucosa (TM) and in mucosa distant from tumors. Lectin reactivity observed in mucosa of DMH-treated rats was compared with that obtained in colon mucosa of control rats. In tumors and non-neoplastic mucosa of DMH-treated rats the reactivity of DBA, SBA, WGA, LFA, GS-I and Con A were similar to that in the mucosa of control rats. In contrast, important changes were observed in the reactivity of UEA-I and PNA. Contrary to the staining in the control mucosa, UEA-I bound intensely to all carcinomas and PNA to 50% and 60% of carcinomas arising in proximal and distal colon, respectively. Moreover, in TM and mucosa distant from tumors, UEA-I and PNA also differed in their binding patterns to that obtained in the colonic mucosa of the control rats. UEA-I- and PNA-binding to luminal surface and UEA-I-binding to the mucin of distal colonic mucosa from DMH-treated rats was similar to that observed in rat fetal colon suggesting a reappearance of a fetal-type pattern. Contrarily, PNA-reactivity in goblet cell and carcinoma mucin is a unique feature of colonic carcinogenesis not present during fetal development.
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PMID:Lectin-binding sites in neoplastic and non-neoplastic colonic mucosa of 1,2-dimethylhydrazine-treated rats. 268 74

A murine mRNA (provisionally called 2ar) is described whose abundance is greatly increased by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate both in JB6 epidermal cells in vitro and in epidermis in vivo. We have previously shown induction of 2ar in epidermal or fibroblast cell lines by tumor promoters, growth factors, and transformation with H-ras. The 2ar mRNA appears to be derived from a single copy gene. It encodes the mouse homolog of rat osteopontin, a 41.5-kDa glycosylated bone phosphoprotein that binds to fibroblasts and osteosarcoma cells and to hydroxylapatite (bone matrix). The rat and mouse sequences are 84% identical at the amino acid level and 87% identical at the nucleotide level. Many of the primary structural features are conserved, including a run of 9-10 aspartic residues and a Gly-Arg-Gly-Asp-Ser cell adhesion sequence. Antiserum raised against portions of the predicted polypeptide immunoprecipitated proteins of apparent Mr 55,000-70,000 both from reticulocyte lysates containing the translation products of hybrid-selected mRNA and from cell culture medium containing metabolically labeled proteins secreted by JB6 cells. The results presented here demonstrate that osteopontin is identical to a transformation-associated phosphoprotein whose level of expression by cultured cells and abundance in human sera has been correlated with tumorigenicity. These results suggest a role for osteopontin in carcinogenesis. The murine version of osteopontin has been given the formal name "secreted phosphoprotein 1" and the designation spp.
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PMID:Osteopontin, a transformation-associated cell adhesion phosphoprotein, is induced by 12-O-tetradecanoylphorbol 13-acetate in mouse epidermis. 272 55

The responses of male noninbred rat colonic epithelial ornithine decarboxylase (EC 4.1.1.17) (ODC) and S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50) (SAMD) activities following topical administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or bile salts were studied. A single intrarectal installation of 13 mumol of MNNG resulted in a significant (p < 0.001) 20-fold peak ODC activity after 4 hr, with a prompt return to control levels by 12 hr. Stimulation of SAMD activity was less pronounced but significant (p < 0.01), with a broad 2-fold peak over controls. No significant responses of colonic epithelial enzyme activities were detected following a single intrarectal instillation of N-methyl-N'-nitroguanidine, a noncarcinogenic and nonmutagenic metabolite of MNNG, at a dose equimolar to that of MNNG. Bile salts significantly (p < 0.001) induced ODC with almost the same kinetic pattern as that observed after MNNG administration in the following order: sodium deoxycholate > sodium chenodeoxycholate > sodium cholate. Activations of SAMD were similar for these 3 bile salts. Glycine- or taurine-conjugated deoxycholate showed ODC and SAMD enzyme activations similar to that of nonconjugated deoxycholate. No significant enzyme response was seen after sodium dehydrocholate treatment. Stimulation of activities of both enzymes was directly dependent on bile salt dose. Induced ODC and SAMD activities were principally localized in colonic epithelium. Deoxycholate-stimulated enzyme activities were significantly inhibited by cycloheximide. Enzyme stimulations by active compounds were accompanied by morphological changes such as mucosal cell degeneration, mucus depletion, submucosal congestion, and punctate hemorrhage, followed by submucosal leukocytic cellular infiltration. These data support the concept that initiating and promoting events may be involved in colon carcinogenesis.
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PMID:Early induction of rat colonic epithelial ornithine and S-adenosyl-L-methionine decarboxylase activities by N-methyl-N'-nitro-N-nitrosoguanidine or bile salts. 744 10

This study presents the physical characterization of mutants induced in mammalian cells by high linear energy transfer alpha-particle radiation that simulates exposure to radon daughters. Alpha-Particles from accelerated 4He at 150 keV/microns were used to induce 20 Chinese hamster ovary mutants that are deficient in dihydrofolate reductase (DHFR) activity. Parental cells were the hemizygous UA21 line. Cell survival decreased exponentially in response to radiation dose from 0.25 to 1.75 Gy. Mutants were obtained at 1.0 (17/20) and 1.25 Gy (3/20); treatments at 1.50 Gy failed to yield mutants. The induced frequency of mutation was 2.3 x 10(-6) at the 1.0 Gy dose, approximately 18-fold greater than the spontaneous mutation rate at this locus. DNA of the 20 confirmed null mutants were examined for alterations in the 25 kb DHFR gene by Southern blotting using a mixed probe that scans a continuous 34 kb of sequence. Deletions were the most prevalent induced change (18/20). Of the two point mutants, DNA sequencing showed that one carries a T:A-->G:C base substitution that changed Val135 to Gly in exon 5; carcinogen-induced reversion to a DHFR+ phenotype at a frequency of 3 x 10(-6) confirmed that the other also carried a single base change. The distribution of deletion break sites in the DHFR locus was non-random. In half of the mutants deletion break sites were clustered within a single 9.4 kb DHFR intron. Fine mapping within the gene of 14 mutants by Southern blotting localized 10 distinct break sites to small restriction fragments (< 2 kb). Results of this mapping indicated that three unequivocally independent mutants apparently arose by the same deletion and that others shared single break sites. Deletion sizes in these mutants were determined by Southern analysis using six cosmids and two plasmid probes that together span approximately 500 kb of sequence in the region of the DHFR locus. Probing blots with the cosmids defined a maximal deletion size in 15/17 mutants and confirmed that deletions extended < 150 kb in 11, a qualitatively different result from that previously obtained after a similar analysis of gamma-ray-induced DHFR- mutants. Since deletions were non-randomly distributed, typically less than replicon size and spared regions containing matrix attachment sites, the results suggest a model whereby alpha-particles induce double-strand breaks in accessible chromatin loops.
Carcinogenesis 1995 Aug
PMID:Non-random deletions at the dihydrofolate reductase locus of Chinese hamster ovary cells induced by alpha-particles simulating radon. 763 30

Gene mutation and abnormal expression of ras oncogenes and p53 gene have a direct bearing on the carcinogenesis. Polymerase chain reaction (PCR), sequencing technique of ds DNA cycle and sequencing system were used to detect the gene mutation of N-ras as well as the exon 5 and 7 of p53 gene in hLA and LTEP-a2 cell lines of human lung adenocarcinoma. The result showed that mutation of both cell lines occurred on the 154th codon in exon5 of p53 gene, where GGC was displaced by GTC resulting a substitution of Val for Gly, nevertheless, N-ras oncogene and the exon7 of p53 gene are normal.
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PMID:[Sequence analysis of N--ras and p53 gene mutation in the human lung adenocarcinoma cell lines]. 772 Jan 10

The role of alkylation of the N3 position of adenine in the cytotoxicity of alkylating agents in mammalian cells is still undefined. By co-transfecting NIH3T3 murine fibroblast and murine B78 H1 melanoma cells with pSG5tag and pSV2neo, we obtained clones expressing the mRNA of the bacterial tag gene coding for N3-methyladenine-DNA glycosylase I (Gly I), which specifically repairs N3-methyladenine. The levels of Gly I were 400 times higher in NIH3T3 pSG5tag (clone 3.9.4) and 12-33 times higher in B78 H1 tag clones (2A4, 2A6, 2C3 and 2D1) than in the respective control cells. The sensitivity to alkylating agents was evaluated in tag-expressing cells in comparison with pSG5, pSV2neo co-transfected control cells. As regards the cytotoxic activity of methylating agents (N-methylnitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine, dimethylsulfate and temozolomide) and other alkylators with different structure and different interactions with DNA such as CC-1065 and FCE-24517 (minor groove binders known to bind to N3 of adenine), 4-[bis(2-chloroethyl)amino]-L-phenylalanine and cis-diamminedichloroplatinum II, cytotoxicity was the same for tag-expressing and non-expressing cells. These results suggest that the increased expression of N3-methyladenine-DNA glycosylase is not necessarily a crucial mechanism for the resistance of cells to alkylating agents.
Carcinogenesis 1994 Mar
PMID:3T3 NIH murine fibroblasts and B78 murine melanoma cells expressing the Escherichia coli N3-methyladenine-DNA glycosylase I do not become resistant to alkylating agents. 811 39

The effects of tripeptide colon mitosis inhibitor (CMI, pGlu-His-Gly-OH) on the proliferation of tumoral cells of dimethylhydrazine (DMH)-induced colonic cancers in rats were studied. Additionally, the effects of CMI on hyperplastic colonic crypts in DMH-treated rats and on normal colonic crypts in carcinogen-untreated rats were estimated. As an index of the cell proliferation the incorporation of bromodeoxyuridine (BrDU) into cell nuclei was used. It was found that the tripeptide significantly suppressed the proliferation of the colonic crypts in normal, carcinogen-untreated rats. However, it failed to suppress the cell proliferation of DMH-induced colonic adenocarcinomas or adenomas and produced only a slight, statistically insignificant decrease of the BrDU labelling index in hyperplastic colonic mucosa of DMH-treated rats. These findings suggest that the process of carcinogenesis might 'switch off' the local negative control of the colonic cell proliferation exerted by endogenous CMI.
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PMID:Failure of tripeptide colon mitosis inhibitor to suppress the cell proliferation of dimethylhydrazine-induced colonic cancers in rats. 818 5


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