Enhanced induction of SV40 replication from transformed mammalian cells by fusion with UV-irradiated untransformed cells

Lübbe, Jann; Drunen, Cornelis M. van; Hertoghs, J.J.L.; Cornelis, Jan J.; Rommelaere, Jean; Eb, A. J. Van Der

doi:10.1016/0027-5107(85)90175-7

Cited by 9 publications

(5 citation statements)

References 23 publications

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“…Elucidation of the molecular basis of alterations of the DNA synthesis machinery may help us to understand the cellular control mechanisms which normally prevent reinitiation in a single cell cycle (16). A number of reports involving cell fusion experiments have shown that trans-acting cellular factors controlling selective amplification of viral sequences such as SV40 or polyomavirus DNA are activated in genotoxically treated cells (32,40,41,44,62).…”

Section: Discussionmentioning

confidence: 99%

“…The notion that various genotoxic agents not only induce selective DNA amplification (SDA) of cellular sequences (for reviews, see references 1, 51, and 55) or persisting viral sequences of known DNA tumor viruses (19,31,36,52,53) but also induce amplification of AAV DNA suggests that these processes may be triggered by the same inducible cellular trans-acting factors recognizing regulatory cis elements within the respective origins of replication. Cell fusion experiments provide further evidence for the role of inducible cellular trans-acting factors in SDA (32,40,44,62). Furthermore, the amplification of both integrated viral sequences (e.g., SV40) and parvoviral DNA is sensitive to aphidicolin, thus indicating involvement of the cellular DNA polymerase ot or 8 in SDA (19).…”

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confidence: 81%

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Origin of adeno-associated virus DNA replication is a target of carcinogen-inducible DNA amplification

Yalkinoglu

Zentgraf

Hübscher

1991

J Virol

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DNA amplification of the helper-dependent parvovirus AAV (adeno-associated virus) can be induced by a variety of genotoxic agents in the absence of coinfecting helper virus. Here we investigated whether the origin of AAV type 2 DNA replication cloned into a plasmid is sufficient to promote replication activity in cells treated by the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). A pUC19-based plasmid, designated pA2Y1, which contains the left terminal repeat sequences (TRs) representing the AAV origin of replication and the p5 and p19 promoter but lacks any functional parvoviral genes is shown to confer replication activity and to allow selective DNA amplification in carcinogen-treated cells. Following transfection of plasmid pA2Y1 or plasmid pUC19 as a control, density labeling by a bromodeoxyuridine and DpnI resistance assay suggested a semiconservative mode of replication of the AAV origin-containing plasmid. Furthermore, the amount ofDpnI-resistant full-length pA2Y1 DNA molecules was increased by MNNG treatment of cells in a dose-dependent manner. In addition, DNA synthesis of plasmid pA2Y1 was studied in vitro. Extracts derived from MNNG-treated CHO-9 and L1210 cells displayed greater synthesis of DpnI-resistant full-length pA2Y1 molecules than did nontreated controls. Experiments with specific enzyme inhibitors suggested that the reaction is largely dependent on DNA polymerase a, DNA primase, and DNA topoisomerase I. Furthermore, restriction endonuclease mapping analysis of the in vitro reaction products revealed the occurrence of specific initiation at the AAV origin of DNA replication. Though elongation was not very extensive, extracts from carcinogen-treated cells markedly amplified the AAV origin region. Our results, including electron microscopic examination, suggest that the AAV origin/terminal repeat structure is recognized by the cellular DNA replicative machinery induced or modulated by carcinogen treatment in the absence of parvoviral gene products.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 81%

Origin of adeno-associated virus DNA replication is a target of carcinogen-inducible DNA amplification

Yalkinoglu

Zentgraf

Hübscher

1991

J Virol

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“…In the light of the notion that DNA-damaging agents, or the inhibitor of dihydrofolate reductase MTX, not only enhance the frequency of SDA of cellular sequences but also induce amplification of parvoviral DNA, suggests that both processes may be mediated by the same inducible cellular trans-acting factors for which both cellular and parvoviral origins or regulatory sequences may compete. Cell fusion experiments seem to support the role of inducible cellular trans-acting factors in SDA (Nomura and Oishi, 1984;Van der Lubbe et al, 1985;Lambert et al, 1986;Lucke-Huhle and Herrlich, 1987).…”

Section: Discussionmentioning

confidence: 89%

Inhibition of N‐methyl‐N′'‐nitro‐n‐nitrosoguanidine‐induced methotrexate and adriamycin resistance in CHO cells by adeno‐associated virus type 2

Yalkinoglu

Schlehofer

Hausen

1990

Intl Journal of Cancer

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We studied the effects of helper-dependent parvovirus AAV [adeno-associated virus] type 2 on carcinogen-inducible resistance to methotrexate (MTX) and adriamycin (ADR) in Chinese hamster ovary cells. Both types of drug resistance were monitored by determination of the number of drug-resistant colonies normalized for the respective value of plating efficiency under non-selective conditions. Treatment of cells with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) drastically enhanced the frequency of resistance to MTX and ADR. By contrast, infection of cells with AAV-2 prior to treatment with MNNG markedly inhibited carcinogen-induced drug resistance. Infection by AAV alone did not exert any effect. Analysis of the dihydrofolate reductase (dhfr) gene copy numbers of individual MTX-resistant clones derived from MNNG-treated and non-treated cultures revealed similar frequencies (60-80%) and amplitudes of dhfr gene amplification (2- to 8-fold) irrespective of prior AAV treatment. Hence, carcinogen-induced enhancement of MTX-resistance could reflect an increase in the frequency of dhfr gene amplification among the survivors of MNNG treatment. On the other hand, inhibition of carcinogen-inducible drug resistance by AAV suggests an interference of the virus with cellular responses to genotoxic stress, thus leading to enhanced cell killing under altered growth conditions. Possible mechanisms responsible for the inhibitory effect of AAV and its relevance in relation to tumor chemotherapy are discussed.

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“…Trans-acting factors have been shown to influence the expression of DNA viruses in other systems. For example, chemical carcinogen-induced asynchronous replication of pollyoma DNA (Lambert et al, 1986) and UV-enhanced SV40 replication in transformed mammalian cells (van der Lubbe et al, 1985) are mediated by trans-acting or "permissiveness" factor(s), respectively. That enhancement occurred in the absence of induced cell fusion suggests that UV-induced trans-acting factors can communicate and be extracellular in nature (Schorpp et al, 1984).…”

Section: Discussionmentioning

confidence: 99%

Chemical carcinogen epstein‐barr virus (ebv) synergism: Ebv genome amplification and site‐specific mutation during transformation

Henderson

Franks

Fronko

1989

Intl Journal of Cancer

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When treated with chemical carcinogens, peripheral blood lymphocytes (PBLs) from normal adults or patients with acquired immunodeficiency syndrome (AIDS) were more readily transformed than non-treated PBLs into immortalized lymphoblastoid cell lines (LCLs) by the Epstein-Barr virus (EBV, FF41-1). Chemical carcinogens also enhanced spontaneous transformation in both PBL populations. Co-cultivation of lethally ultraviolet (UV)-irradiated uninfected PBLs with EBV-infected PBLs resulted in a dose-related enhancement of transformation, providing evidence that enhancement is in part mediated by carcinogen-induced diffusible trans-acting factors. Analysis of the EcoRI J region of resident EBV genomes showed that LCLs established from carcinogen-treated PBLs frequently had EBV genome amplification higher than that seen in controls. Carcinogen-induced EBV genome amplification was shown to be dose-related. The organization of the terminal region of the EBV genome was analyzed in LCLs derived from carcinogen-treated PBLs and compared to that of FF41-1 and B95-8. LCLs established from N-methyl-N'-nitroso-nitrosoguanidine (MNNG)- and aflatoxin B1-treated PBLs frequently had 2 circular forms of the EBV genome and several linear forms varying by numbers of terminal repeats (TRs) at the 3' and 5' end. This is in contrast to the single episomal circular and linear form of the EBV genome found in the parent FF41-1 and single episomal circular form in control FF41-1-carrying LCLs. Linear forms of the EBV genome were only found in FF41-1-transformed LCLs derived from carcinogen-treated PBLs and were associated with the production of unusually large amounts of infectious EBV. These results demonstrate that chemical carcinogen-mediated enhancement of transformation is accompanied by quantitative and qualitative alterations in the physical structure, organization and expression of the EBV genome which may in turn be the result of a carcinogen-induced cellular SOS response.

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Enhanced induction of SV40 replication from transformed mammalian cells by fusion with UV-irradiated untransformed cells

Cited by 9 publications

References 23 publications

Origin of adeno-associated virus DNA replication is a target of carcinogen-inducible DNA amplification

Origin of adeno-associated virus DNA replication is a target of carcinogen-inducible DNA amplification

Inhibition of N‐methyl‐N′'‐nitro‐n‐nitrosoguanidine‐induced methotrexate and adriamycin resistance in CHO cells by adeno‐associated virus type 2

Chemical carcinogen epstein‐barr virus (ebv) synergism: Ebv genome amplification and site‐specific mutation during transformation

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