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

We assessed the possibility to detect promoters of bladder carcinogenesis by a short-term in vitro assay utilizing the activation of Epstein-Barr virus (EBV) expression in EBV genome-carrying human lymphoblastoid cells. This system is composed of EBV-nonproducer Raji cells as the indicator, n-butyrate as the EBV-inducer and the test substance. None of eight known bladder carcinogens (2-naphthylamine, 2-acetylaminofluorene, N-butyl-N-(4-hydroxybutyl)nitrosamine, N-butyl-N-(3-carboxypropyl) nitrosamine, N-methyl-N-nitrosourea, N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide, benzidine, cyclophosphamide) or five promoters (sodium saccharin, sodium cyclamate, urea, allopurinol, DL-tryptophan) were detected by this system. Normal urine from 20 rats did not activate the EBV genome. Neither the 0.45 micron membrane filtrates nor ether extracts of urine obtained from rats given one of 4 bladder carcinogens, 4 promoters or phorbol 12-myristate 13-acetate reacted with this system, whereas those from rats given either vincristine or vinblastine did, although their activity for promoting bladder carcinogenesis is not known. Urine samples from 42 patients with bladder cancers, when tested as filtrates, ether extracts or XAD-2 resin adsorbates, did not activate EBV expression. These results suggest that EBV-activating substances contribute little to promotion of bladder carcinogenesis and that this test might not be applicable for screening of tumor promoters in urine.
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PMID:[Failure to activate Epstein-Barr virus genome in a latently-infected human lymphoblastoid cell line with urine containing a bladder carcinogenesis promoter]. 609 26

N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) is a potent carcinogen that alkylates nucleic acids. Interaction of MNNG with human lymphoblastoid cell lines carrying Epstein-Barr virus (EBV) was studied. Treatment of virus-producing cells (P3HR-1) with MNNG resulted in an approximately 3-fold increase in EBV genome copies per cell as determined by cRNA--DNA hybridization. This effect was not observed in a non-virus-producer line (Raji). Dose-response studies indicated that the optimum concentration was between 0.5 micrograms and 2 micrograms/ml. This same dose range was most effective in inhibiting cell proliferation both of P3HR-1 and Raji cells. Concomitant treatment of P3HR-1 cells with MNNG and 12-O-tetradecanoylphorbol-13-acetate gave an additive increase to 9-fold of the number of EBV genome copies per cell. Pretreatment of Raji cells with MNNG followed by superinfection with P3HR-1 virus resulted in a 35% enhancement of EBV DNA replication as analyzed by density centrifugation. In contrast, Raji cells superinfected with MNNG-treated EBV showed a marked reduction in EBV DNA replication which indicates that the lesions produced in the viral genome by the drug interferred with the infectious potential of the virus.
Carcinogenesis 1983
PMID:Enhancement of replication of Epstein-Barr virus DNA in human lymphoblastoid cell lines by N-methyl-N'-nitro-N-nitrosoguanidine. 629 23

Teleocidin, a new potent tumor promoter, produces biological effects similar to 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on human lymphoblastoid cell lines. A wide range of concentrations (4-16 ng/ml) of teleocidin were optimal for induction of replication of latent Epstein-Barr virus (EBV) genomes in P3HR-1 cells; cell growth was significantly inhibited in this dose range. In contrast, treatment of Raji cells with an identical dose range of teleocidin did not induce replication of latent EBV genomes. As with TPA, P3HR-1 cells in the stationary phase were twice as responsive to teleocidin induction as exponentially growing cells. The activation of P3HR-1 cells both by teleocidin and TPA greatly enhanced the synthesis of EBV DNA and EBV-associated polypeptides as determined by cRNA - DNA hybridization and by analysis on polyacrylamide gels. Both drugs also increased production of biologically active virus as monitored by the synthesis of viral DNA in superinfected Raji cells. These effects were completely inhibited by retinoic acid. However, retinoic acid did not inhibit the spontaneous viral DNA replication that occurs in P3HR-1 cells not treated with the inducers. Thus, it appears that retinoic acid antagonizes the inducing effects of TPA and teleocidin, but not viral replication itself.
Carcinogenesis 1984 Apr
PMID:Antagonistic action of retinoic acid against teleocidin and 12-O-tetradecanoyl-phorbol-13-acetate on activation of Epstein-Barr virus genomes. 632 48

Fifteen established tumor promoters belonging to different chemical groups were tested for their ability to induce Epstein-Barr virus (EBV)-specific early antigens (EA) in EBV-genome-positive nonproducer Raji cells. Saccharin (a promoter in urinary bladder carcinogenesis), DDT (a promoter in liver carcinogenesis), anthralin and iodoacetic acid (promoters in skin carcinogenesis) gave a significant induction with a maximum of induced cells of 20% (8 mg/ml), 0.8% (20 micrograms/ml), 0.8% (100 ng/ml) and 0.7% (0.4 micrograms/ml), respectively. In addition, after combined application with a noninducing dose (0.2 ng/ml) of 12-O-tetradecanoyl-phorbol-13-acetate (TPA), seven additional tumor promoters induced 0.3-2.1% EA-positive cells two days after treatment. The results indicate that in addition to mouse skin tumor promoters such as diterpene esters, several compounds reported to possess tumor-promoting activity in other types of tissue induce EBV. The data suggest that EBV induction is an effect commonly exerted by this group of compounds which should be very useful in screening for environmental tumor promoters.
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PMID:Induction of Epstein-Barr virus antigens by tumor promoters for epidermal and nonepidermal tissues. 632 26

5-Methyl-2'-deoxycytidine (m5dC) levels were measured in DNA from three types of cultured cells following treatment with u.v. radiation and two chemical carcinogens, N-methyl-N-nitrosourea (MNU) and N-acetoxy-2-acetylaminofluorene (NA-AAF). Control values for m5dC in Raji cells (a human lymphoblastoid cell line), S49 cells (a mouse thymic lymphoma cell line) and human diploid fibroblasts are 3.6%, 3.6% and 3.2%, respectively. None of the damaging agents produced a detectable change in methylation levels of newly replicated DNA, even at levels of damage that inhibited replication by 95%. In contrast, treatment with 5-aza-2'-deoxycytidine, a known methyltransferase inhibitor, transiently reduced genomic methylation by 89% and 74% in Raji and S49 cells, respectively. Although other investigators have found a marked reduction in m5dC in DNA replicated after carcinogen treatment, our experiments indicate that extensive demethylation is not a necessary consequence of DNA damage.
Carcinogenesis 1984 Sep
PMID:Methylation of deoxycytidine in replicating cells treated with ultraviolet radiation and chemical carcinogens. 646 3

Human Raji lymphoblast-like cells were propagated in the presence of various concentrations of N-methyl-N-nitrosourea (MNU) and the degree of enzymatic methylation of newly synthesized DNA was analysed by two independent methods. The overall extent of enzymatic DNA methylation was measured on the basis of [14C]deoxycytidine derived radioactivity incorporated into DNA 5-methylcytosine and cytosine residues. Enzymatic methylation of internal cytosines at 5'-CCGG-3' sequences of Raji DNA was analysed by use of the bacterial restriction enzyme HpaII and its isoschizomer MspI. The data obtained by both methods indicate that the treatment with MNU causes a lower level of enzymatic methylation of newly synthesized DNA. This lower extent of DNA methylation persists in the absence of the carcinogen in the cell cycles following the treatment.
Carcinogenesis 1981
PMID:Hypomethylation of DNA in Raji cells after treatment with N-methyl-N-nitrosourea. 727 86

The Raji human lymphoma line is able to remove O6-methylguanine (O6MeG) lesions introduced by treatment of cells with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The reaction has a rapid phase in which approximately 40% of the O6MeG is removed in the first 10 min. The capacity of cells for rapid O6MeG removal is limited and is saturated at concentrations of MNNG which do not saturate the systems removing 3-methyladenine. Pretreatment of cells with MNNG inhibits their ability to remove O6MeG produced by a subsequent dose given after 2 h. Treatment with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) is effective in diminishing cellular capacity for O6MeG removal, and cells unable to remove O6MeG and sensitive to the cytotoxic effects of MNNG are also more sensitive to ENNG than their removal competent counterparts. Regeneration of the ability to remove O6MeG requires incubation of cells for periods greater than 24 h. The O6MeG removal system is similar to that found in adapted Escherichia coli although the capacity of the Raji lymphoma line much lower than that of the induced bacteria per unit of DNA.
Carcinogenesis 1981
PMID:Limited capacity for the removal of O6-methylguanine and its regeneration in a human lymphoma line. 732 30

To search for possible anti-tumor-promoters (chemopreventive agents), we carried out a primary screening of 21 euglobals (acylphloroglucinol-monoterpene or -sesquiterpene structures) isolated from the juvenile leaves of five species of Eucalyptus plants using an in vitro synergistic assay system. Of these compounds, euglobal-G1--G5 (1-5), -Am-2 (15) and -III (16) exhibited significant inhibitory effects on Epstein-Barr virus (EBV) activation induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, the effects of compounds 1 and 16 on the cell cycle of Raji cells were also examined by a flow cytometer, and both compounds 1 and 16 exhibited strong inhibition on the effect of the cell cycle induced by TPA. These two euglobals (1 and 16) exhibited remarkable anti-tumor-promoting effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.
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PMID:Anti-tumor-promoting activities of euglobals from Eucalyptus plants. 755 98

To answer the question whether the level of p53 expression also reflects the status of a cell, with reference to transformation and genome stability, we have examined, by immunocytochemistry, the presence of p53 protein in a number of cell types including human diploid cells, Chinese hamster embryonal cells at different passages and gene amplified and/or transformed Chinese hamster cell lines. Primary human fibroblasts at early passage (LEO) and an established, non transformed, Chinese hamster cell line at early passage (CHEF/18) did not show any detectable p53 expression, either nuclear or cytoplasmic. All transformed human (Raji) and Chinese hamster cell lines (CHO, V79, V79/B7) showed a nuclear expression of p53, although at different intensities. Two cell lines selected from V79/B7 for their resistance to phosphonacetyl-L-aspartate or methotrexate and previously shown to bear gene amplification, showed p53 expression. In PALA L cells p53 expression was nuclear as in other positive cell lines tested, while in MTX M cells it was cytoplasmic. CHEF/18 cells at late passage in culture showed the typical behaviour of transformed cells and p53 was detected in several cells. Moreover, when transformed CHO cells were treated with compounds known to induce reverse transformation, both the disappearance of hallmarks of transformed phenotype and p53 reduction were observed. These results indicate a strong association within the same cell type between p53 expression and transformed status.
Carcinogenesis 1995 Oct
PMID:p53 expression in normal versus transformed mammalian cells. 758 48

Human endogenous retroviruses (HERVs) are widely believed to represent possible pathogenic agents in autoimmune disorders and carcinogenesis. We generated 2 monoclonal antibodies (mAbs) against a recombinant HERV-K outer-membrane envelope protein. These mAbs were capable of immunoprecipitating protein bands of 55, 51 and 45 kDa, respectively, from [35S]methionine-labeled lysates of T47D (human breast carcinoma), Raji, Bjab (both human beta-lymphoblastoid) and H9 (human T-cell lymphoma) cells. Furthermore, the 55 kDa band could be precipitated from cell-free supernatant of biosynthetically labeled T47D cells, indicating that this molecule may be secreted. Indirect immunofluorescence and subsequent FACS analysis demonstrated the presence of these molecules on T47D, HeLa, Raji, Bjab and H9 cells as well as on lymphocytes isolated from tonsils and stimulated with poke weed mitogen (PWM). Due to the broad distribution and lack of detection of HERV-K-env mRNA in these cells, we believe that these antigens are of cellular origin detected by crossreactivity of mAbs against HERV-K-env protein with cellular molecules.
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PMID:Reactivity of monoclonal antibodies established against a recombinant human endogenous retrovirus-K (HERV-K) envelope protein. 759 Sep 8


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