Transformation of C3H/10T1/2 CL8 mouse embryo fibroblasts by ultraviolet irradiation and a phorbol ester

Mondal, Shreya; Heidelberger, Charles

doi:10.1038/260710a0

Cited by 145 publications

(46 citation statements)

References 7 publications

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“…There is evidence that PD promote malignant transformation directly, i.e., independent of effects on host defense. Thus, PD tumor promoters increase the transformation in culture of normal cells by benzo(a)pyrene, malignant viruses, or ultraviolet irradiation (18)(19)(20). They also alter the cytoskeletal structure of cultured cells (21,22) and may inhibit or accelerate differentiation of certain cell lines (23,24).…”

Section: Introductionmentioning

confidence: 99%

Natural killing of tumor cells by human peripheral blood cells. Suppression of killing in vitro by tumor-promoting phorbol diesters.

Seaman¹,

Gindhart²,

Blackman³

et al. 1981

J. Clin. Invest.

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A B S T R A C T Tumor-promoting phorbol diesters were shown to suppress natural killing in vitro by human peripheral blood mononuclear cells. The inhibitory effect of different phorbol diesters and their analogues correlated with their potency as tumor promoters, the most effective agent being 12-0-tetradecanoylphorbol-13-acetate (TPA). Both peripheral blood cells and targets specifically bound TPA, and natural killing could be inhibited by pretreatment of either cell population with TPA, though this was less effective than direct addition of TPA to the assay. Cells that had been pretreated with TPA released TPA and metabolites of TPA during subsequent incubation in fresh medium. This release of TPA was evidently responsible for the inhibition of natural killing by pretreated target cells; in experiments where labeled and unlabeled target cells were mixed, pretreatment of unlabeled targets with TPA inhibited killing of labeled targets. Suppression of natural killing by TPA was greatly reduced when adherent cells were removed from the peripheral blood cells, suggesting that monocytes mediate suppression. Inhibition of natural killing by TPA provides a model for examining the regulation of natural killing. Suppression of natural killing by phorbol diesters may contribute to their activity as tumor promoters.

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Section: Introductionmentioning

confidence: 99%

Natural killing of tumor cells by human peripheral blood cells. Suppression of killing in vitro by tumor-promoting phorbol diesters.

Seaman¹,

Gindhart²,

Blackman³

et al. 1981

J. Clin. Invest.

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show abstract

“…Some of the phorbol esters-in particular, 12-O-tetradecanoylphorbol 13-acetate (TPA)-are extremely potent tumor promoters in the mouse skin model (28,29). TPA was also shown recently to increase the efficiency ofcarcinogen-, virus-, or radiation-induced transformation of cultured mouse cells (45)(46)(47).…”

mentioning

confidence: 99%

On the possibility of metabolic control of replicon "misfiring": relationship to emergence of malignant phenotypes in mammalian cell lineages.

Varshavsky¹

1981

Proc. Natl. Acad. Sci. U.S.A.

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Constraints of a multireplicon chromosomal organization and of the necessity to maintain constant gene dosages demand that each origin of replication in a eukaryotic cell "fire" (initiate replication) only once per cell cycle. The central idea of this work is that a low probability of an extra ("illegitimate") round of DNA replication (called below "replicon misfiring") within any given chromosomal domain could be increased by certain substances of either intra-or extracellular origin. The term "firone" is proposed for such a substance. It is shown that existence of firones could greatly speed up evolution of cellular systems under selection pressure, a developing tumor being one example of such a system. Experimentally testable predictions of the firone hypothesis are discussed.One feature ofeukaryotic DNA replication is tight control ofthe number ofinitiation events per origin ofreplication. Apart from a few special cases (2-5), each origin of replication in a eukaryotic cell fires only once per cell cycle; repetitive firings at the same origin are prevented, apparently by a special mechanism (6-8). Reasons for the tight control of the frequency of replication initiation include constraints imposed by a multireplicon chromosomal organization, by complex mitotic mechanisms, and by the necessity to maintain constant gene dosages for at least some ofthe genes. Molecular mechanisms for suppression of extra rounds of DNA replication are unknown and may include specific chromatin structures at the replication origins or termini and possibly replication-dependent chemical modifications of DNA segments involved in replication initiation.The important point, however, is that the probability of an extra ("illegitimate") round of DNA replication (called below "replicon misfiring") within any given chromosomal domain, although generally very low, is not zero, as indicated by the following lines of evidence.

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“…The culture system used in the present study is fibroblastic whereas well characterized two-stage systems are also epithelial. The end point analyzed in the present study seemed to be a late irreversible event in carcinogenesis since the foci are irreversibly growing and tumourigenic (Mondal & Heidelberger, 1976) in contrast to the papillomas produced in the well-characterized epidermal system in vivo which are reversibly growing (Burns et al, 1978) and the cells from which are non-tumourigenic (Pera & Gorman, 1984). Moreover, TPA has not been demonstrated to influence any of the irreversible steps in epidermis in vivo (Verma & Boutwell, 1980).…”

Section: Resultsmentioning

confidence: 87%

“…A number of systems have been proposed as models for in vitro promotion; of these mouse embryo fibroblast C3H/IOT1/2 cells have been well characterized (Reznikoff et al, 1973;Mondal & Heidelberger, 1976;Lillehaug & Djurhuss, 1982). Exposure of these cells at low density to carcinogenic agents such as polycyclic hydrocarbons, ultra-violet irradiation or X-rays at subcarcinogenic doses followed by sustained exposure to phorbol esters such as TPA results in augmented formation of transformed foci.…”

Section: Resultsmentioning

confidence: 99%

The tumour promoter 12-O-tetradecanoylphorbol-13-acetate increases the activities of some peroxisome-associated enzymes in in vitro cell culture

Berge¹

1986

Br J Cancer

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Transformation of C3H/10T1/2 CL8 mouse embryo fibroblasts by ultraviolet irradiation and a phorbol ester

Cited by 145 publications

References 7 publications

Natural killing of tumor cells by human peripheral blood cells. Suppression of killing in vitro by tumor-promoting phorbol diesters.

Natural killing of tumor cells by human peripheral blood cells. Suppression of killing in vitro by tumor-promoting phorbol diesters.

On the possibility of metabolic control of replicon "misfiring": relationship to emergence of malignant phenotypes in mammalian cell lineages.

The tumour promoter 12-O-tetradecanoylphorbol-13-acetate increases the activities of some peroxisome-associated enzymes in in vitro cell culture

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