Increased integration of viral genome following chemical and viral treatment of hamster embryo cells

Casto, Bruce C.; Miyagi, M.; Meyers, Judy; DiPaolo, Joseph A.

doi:10.1016/0009-2797(79)90050-4

Cited by 31 publications

(12 citation statements)

References 17 publications

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“…Comparable results have been obtained in studies employing hamster embryo cells treated with MMS and then infected with SA7 [28,29]. MMS pretreatment did result, however, in an increase in the quantities of SA7 DNA in the total population of hamster embryo cells 2-9 d after MMS treatment and viral infection 1291.…”

Section: Discussionsupporting

confidence: 73%

Enhancement of adenovirus transformation of cloned rat embryo fibroblast cells by gamma irradiation

Zhang

Geard

et al. 1990

Molecular Carcinogenesis

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We have analyzed the effect of gamma irradiation on the induction of morphological transformation of cloned rat embryo fibroblast (CREF) cells by the host-range cold-sensitive type 5 adenovirus mutant, H5hr1. Treatment of CREF cells with 1-6 Gy of gamma irradiation immediately prior to viral infection resulted in dose-dependent decrease in cell survival and concomitant increase in viral transformation frequency. Exposure of CREF cells to 1-6 Gy of gamma radiation alone resulted in a similar dose-dependent inhibition in cell survival but without any subsequent morphological transformation. The effect of gamma irradiation on viral transformation was greatest when cells were irradiated directly before viral infection. The reduction in the enhancement of transformation was both dose and time dependent. The ability of gamma irradiation to enhance viral transformation was substantially reduced if CREF cells were treated with inhibitors of RNA (actinomycin D) and protein (cycloheximide) synthesis. Employing a single-cell colony transfer assay and in situ hybridization with a 32P-labeled Ad5 DNA probe, we found that gamma irradiation of CREF cells prior to infection with H5hr1 resulted, 10 and 17 d after infection and replating, in an increase in the percentage of surviving CREF colonies that contain Ad5 DNA. Analysis of viral DNA integration by DNA-filter hybridization (Southern blot analysis) in H5hr1-transformed CREF clones isolated from untreated and gamma-irradiated cultures indicates that gamma irradiation caused increases in both the number of copies of Ad5 E1A DNA sequences integrated into cellular DNA and the number of unique Ad5 E1A DNA integration sites in transformed cells. These results indicate that gamma irradiation enhancement of adenovirus transformation was a consequence of radiation-induced cellular factors with finite life spans that are mediators of enhanced viral transformation. Potentially important components of the radiation enhancement process appear to involve an alteration in both the retention of free Ad5 DNA in surviving cells and an alteration in the profile of viral-DNA integration in gamma-irradiated cells.

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Section: Discussionsupporting

confidence: 73%

Enhancement of adenovirus transformation of cloned rat embryo fibroblast cells by gamma irradiation

Zhang

Geard

et al. 1990

Molecular Carcinogenesis

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“…In a specific clone of Fischer rat embryo fibroblast (CREF) cells [10,11], pretreatment with methyl rnethanesulfonate (MMS) 2-14 h prior to infection with H5hrl induced enhanced viral transformation, whereas pretreatment of CREF cells with MMS 18 h prior to viral infection resulted in the absence of enhancement of transformation [6,12]. The ability of carcinogens to alter DNA structure and function, as well as induce specific DNA repair processes and stress responses in damaged cells, have been implicated in the ability of diverse carcinogenic agents, including both chemical and physical carcinogens, to induce cellular transformation as well as to increase the frequency of viral transformation [4][5][6]131.…”

Section: Introductionmentioning

confidence: 98%

Enhancement of viral and DNA mediated transformation of cloned rat embryo fibroblast cells by 3‐aminobenzamide

Zhang

Fisher

1990

Molecular Carcinogenesis

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We have analyzed the effect of the poly(ADP-ribose) synthesis inhibitor 3 aminobenzamide (3AB) on de novo and methyl methanesulfonate (MMS) and gamma irradiation enhancement of viral transformation of a cloned rat embryo fibroblast cell line, CREF, by a cold-sensitive host-range mutant of type 5 adenovirus, H5hr1. Additionally, we have evaluated the effect of 3AB on the transformation of CREF cells following transfection with a gene conferring resistance to hygromycin (hygr) or the neomycin analogue G418 (neor) in combination with a cloned type 5 adenovirus E1A transforming gene (Ad5 E1A) or the Ha-ras (T24) oncogene. 3AB induced a dose- and time-dependent increase in the level of de novo MMS-enhanced and gamma irradiation-enhanced transformation of CREF cells by H5hr1, whereas it did not induce morphological transformation in uninfected control, MMS-pretreated, or gamma irradiation-pretreated CREF cells. Temporal kinetic studies indicated that 3AB was most effective in enhancing de novo and MMS-enhanced and gamma irradiation-enhanced viral transformation when applied early after viral and carcinogen plus viral infection and when present for extended time periods (4-5 wk). 3AB also increased the frequency of resistant colonies following transfection with several cloned genes, including hygr, neor, and protein kinase C (which also contained a neor gene), and the frequency of morphological transformation of CREF cells following cotransfection with a hygr gene and an Ad5 E1A or an activated Ha-ras (T24) gene. In contrast, 3AB exerted the opposite effect, i.e., an inhibitory effect, when applied to NIH 3T3 cells transfected with a hygr or neor gene, alone or in combination with a T24 gene. The ability of 3AB to enhance the frequency of transformation of CREF cells was not associated with a selective effect on the growth of H5hr1-transformed CREF cells in monolayer or agar culture. Similarly, 3AB did not alter the percentage of MMS- or gamma irradiated-pretreated H5hr1-infected cells retaining free Ad5 DNA or the random pattern or quantity of viral DNA integration in control or carcinogen-treated H5hr1-transformed cells. These results suggest that cellular processes regulated by the nuclear enzyme ADPRT, or additional processes modified by 3AB, may be important mediators of stable transformation induced by transfected DNA and both de novo and carcinogen-enhanced viral transformation of specific target cells.

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“…A deficiency in this enzyme renders the cell insensitive to the base analogues. Thus, in contrast to bacterial systems which quantitate the reversion of a previously induced mutation, this (56,57). In particular, treatment with polycyclic aromatic hydrocarbons or with alkylating agents significantly enhanced viral transformation as compared to that observed with the virus alone.…”

Section: Metal Mutagenesis In Mammalian Cellsmentioning

confidence: 99%

Effects of metals in in vitro bioassays.

Sirover¹

1981

Environ Health Perspect

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The capacity of in vitro bioassays to detect the potential carcinogenicity of metal compounds is reviewed. The in vitro bioassays discussed include: bacterial reversion analysis to determine the capacity of metal salts to revert SalmoneUa typhimurium histidine auxotrophs or to revert Escherichia coli WP 2 tryp-to tryptophan prototrophy; examination of the ability of metal salts to preferentially inhibit cell growth in Bacillus subtilis cells deficient in DNA repair pathways; determination of the ability of metal salts to induce resistance to base analogs in mammalian cells; the capacity of metal salts to enhance viral transformation of mammalian cells or to transform cells in the absence of virus; and the ability of metal salts to induce chromosomal aberrations in mammalian cells. Using each of these in vitro bioassays, diverse metal compounds have been identified as potential carcinogens. Furthermore, the use of different compounds of a specific metal may allow a determination of the valence which may be required for carcinogenesis.

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Increased integration of viral genome following chemical and viral treatment of hamster embryo cells

Cited by 31 publications

References 17 publications

Enhancement of adenovirus transformation of cloned rat embryo fibroblast cells by gamma irradiation

Enhancement of adenovirus transformation of cloned rat embryo fibroblast cells by gamma irradiation

Enhancement of viral and DNA mediated transformation of cloned rat embryo fibroblast cells by 3‐aminobenzamide

Effects of metals in in vitro bioassays.

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