Significance of treatment interval and DNA repair in the enhancement of viral transformation by chemical carcinogens and mutagens

Casto, Bruce C.; Pieczynski, William J.; Janosko, Nancy; DiPaolo, Joseph A.

doi:10.1016/0009-2797(76)90001-6

Cited by 53 publications

(15 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The addition of TPA could be delayed until after viral uptake and integration of adenovirus sequences into the host genome had occurred, thus indicating that the enhancement by TPA was not exerted on these steps. This is in contrast to the ability of certain initiating carcinogens to enhance DNA virus transformation [15,16,21,22] .…”

Section: Phenotypic Enhancement and Effects On Adenovirus Transformationmentioning

confidence: 77%

Action of phorbol esters in cell culture: Mimicry of transformation, altered differentiation, and effects on cell membranes

et al. 1979

View full text Add to dashboard Cite

The carcinogenic process is usually multifactor in its causation and multistep in its evolution. It is likely that entirely different molecular mechanisms underlie the many steps in this process. In contrast to initiating carcinogens, the action of the tumor-promoting phorbol esters does not appear to involve covalent binding to cellular DNA and they are not mutagenic. Recent studies in cell culture have revealed two interesting biologic effects of the phorbol esters and related macrocyclic plant diterpenes. The first is that at nanomolar concentrations they induce several changes that resemble those seen in cells transformed by chemical carcinogens or tumor viruses. These include altered morphology and increased saturation density, altered cell surface fucose-glycopeptides, decrease in the LETS protein, increased transport of deoxyglucose, and increased levels of plasminogen activator and ornithine decarboxylase. In transformed cells exposed to phorbol esters the expression of these features is further accentuated. Phorbol esters do not induce normal cells to grow in agar but they do enhance the growth in agar of certain transformed cells. The second effect of the phorbol esters is inhibition of terminal differentiation. This effect extends to a variety of programs of differentiation and is reversible when the agent is removed. With certain cell culture systems induction of differentiation, rather than inhibition, is observed. Both the transformation mimetic and the differentiation effects are exerted by plant diterpenes that have tumor-promoting activity but not by congeners that lack such activity. The primary target of phorbol esters appears to be the cell membrane. Early membrane-related effects include enhanced uptake of 2-deoxyglucose and other nutrients, altered cell adhesion, induction of arachidonic acid release and prostaglandin synthesis, inhibition of the binding of epidermal growth factor to cell surface receptors, altered lipid metabolism, and modifications in the activities of other cell surface receptors. A model of "two stage" carcinogenesis encompassing the known molecular and cellular effects of initiating carcinogens and tumor promoters is presented. According to this model, initiating carcinogens induce stable alterations in the cellular genome but these are not manifested until tumor promoters modulate programs of gene expression and induce the clonal outgrowth of the initiated cell.

show abstract

Section: Phenotypic Enhancement and Effects On Adenovirus Transformationmentioning

confidence: 77%

Action of phorbol esters in cell culture: Mimicry of transformation, altered differentiation, and effects on cell membranes

et al. 1979

View full text Add to dashboard Cite

show abstract

“…Although this assay is listed with the transformation assays, Casto et al (45) have reported the significance of DNA damage and repair in the enhancement of viral transformation by chemicals. This assay may be a measure, therefore, of DNA damage.…”

Section: Viral Enhancement Of Transformationmentioning

confidence: 99%

Evaluation of the mutagenicity and carcinogenicity of motor vehicle emissions in short-term bioassays.

Lewtas¹

1983

Environ Health Perspect

View full text Add to dashboard Cite

Incomplete combustion of fuel in motor vehicles results in the emission of submicron carbonaceous particles which, after cooling and dilution, contain varying quantities of extractable organic constituents. These organics are mutagenic in bacteria. Confirmatory bioassays in mammalian cells provide the capability of detecting chromosomal and DNA damage in addition to gene mutations. In order to evaluate the mutagenicity of these organics in mammalian cells, extractable organics from particle emissions from several diesel and gasoline vehicles were compared in a battery of microbial, mammalian cell and in vivo bioassays. The mammalian cell mutagenicity bioassays were selected to detect gene mutations, DNA damage, and chromosomal effects. Carcinogenesis bioassays conducted included short-term assays for oncogenic transformation and skin tumorigenesis. The results in different assay systems are compared both qualitatively and quantitatively. Good quantitative correlations were observed between several mutagenesis and carcinogenesis bioassays for this series of diesel and gasoline emissions.

show abstract

“…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: 97%

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

Zhang

Fisher

1990

Molecular Carcinogenesis

View full text Add to dashboard Cite

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.

show abstract

Significance of treatment interval and DNA repair in the enhancement of viral transformation by chemical carcinogens and mutagens

Cited by 53 publications

References 29 publications

Action of phorbol esters in cell culture: Mimicry of transformation, altered differentiation, and effects on cell membranes

Action of phorbol esters in cell culture: Mimicry of transformation, altered differentiation, and effects on cell membranes

Evaluation of the mutagenicity and carcinogenicity of motor vehicle emissions in short-term bioassays.

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

Contact Info

Product

Resources

About