Two-stage Malignant Transformation of Rat Fibroblasts in Tissue Culture

Lasne, C; Gentil, A.; Chouroulinkov, I

doi:10.1038/247490a0

Cited by 92 publications

(28 citation statements)

References 11 publications

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“…However, one should not forget that the cellular model differs from the animal model because of the earlier " spontaneous transformation " of the control cells. (Lasne et al, 1974), promotion was begun 35 days after initiation, and the results were similar to those presented here.…”

Section: Transformation and Malignancysupporting

confidence: 85%

Two-stage carcinogenesis with rat embryo cells in tissue culture

Lasne¹,

Gentil²,

Chouroulinkov³

1977

Br J Cancer

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Summary.-Transformation of rat embryo fibroblasts in vitro has been investigated using initiation with either benzo(a)pyrene (BaP), 7,12-dimethylbenz(a)anthracene (DMBA) or benzo(e)pyrene (BeP) and promotion with either phorbol ester (TPA) or croton oil (Cr.Oil). The criteria used to assess in vitro transformation were (a) the efficiency of cloning in liquid medium, (b) abnormal cellular morphology and (c) the development of malignant tumours following s.c. inoculation of newborn rats.The results show that the cloning efficiency, which remained low in the control cells, was increased to a variable extent in the treated groups. Transformation occurred in all groups, but occurred earliest in cells that were initiated and promoted. Initiation with DMBA or BaP and promotion with TPA or Cr.Oil led to the earliest acquisition of malignancy. Correlations were found between the transformation of cells in vitro and the acquisition of malignant potential, and between the carcinogenic action of the compounds in vitro and their action in vivo, but cloning efficiency was not a reliable indicator of in vitro transformation or of malignancy. In most cases in vitro transformation appeared to precede the acquisition of malignancy, but in two cases it occurred later. The studies also show that BeP, which is a tumour initiator in vivo, also acts in this way in vitro. The conclusion drawn from a discussion of these results and of two -stage carcinogenesis in vivo is that two -stage carcinogenesis can be reproduced in tissue culture; this model may be useful in studies of those mechanisms of chemical carcinogenesis that involve the processes of initiation and promotion.

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Section: Transformation and Malignancysupporting

confidence: 85%

Two-stage carcinogenesis with rat embryo cells in tissue culture

Lasne¹,

Gentil²,

Chouroulinkov³

1977

Br J Cancer

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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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“…In vitro effects of 12-0-tetradecanoyl-phorbol-13-acetate (TPA) on cellular multiplication, RNA synthesis and DNA repair synthesis have been studied in mouse fibroblasts (Sivak & Van Duuren, 1970;Sivak et al, 1969Sivak et al, , 1972Trosko et al, 1975). More recently, TPA has been shown to enhance the focal transformation rate of mouse C3H/1OT1/2 cells and to enhance transformation in rat fibroblasts in culture (Lasne et al, 1974(Lasne et al, , 1977. The rate of focal transformation in mouse cells could be increased or decreased, depending * To whom requests for reprints should be sent. on the time at which TPA was administered relative to the carcinogen .…”

mentioning

confidence: 99%

Two-stage malignant transformation in hamster embryo cells

Poiley¹,

Raineri²,

Pienta³

1979

Br J Cancer

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Summary.-Transformation of primary hamster embryo cells was investigated using 3-methylcholanthrene (MCA), a combination of MCA and 12-0-tetradecanoylphorbol-13-acetate (TPA), and initiation with MCA or dibenz(a,h)anthracene (DBA) followed by promotion with TPA. Evidence for transformation was (a) abnormal cellular morphology, (b) increased lifespan, (c) growth in soft agar, and (d) tumour induction by s.c. inoculation into suckling hamsters.Cells treated with either MCA or MCA+TPA showed the same latent period to morphological transformation, although their tumorigenic potential varied. Cells did not form tumours when TPA was administered 7 days after treatment with either MCA or DBA. However, when administration of TPA was delayed to 27 days after treatment with a transforming dose of MCA or a subthreshold dose of DBA, the cells transformed and produced tumours in hamsters.Our results show that TPA may act as an inhibitor or promoter, depending on the length of time between treatment of the hamster embryo cells with the carcinogen and administration of the TPA. It appears that treatment of cells with TPA before the initiating event is complete inhibits or delays the development of their ability to induce tumours in animals or grow in soft agar. However, with a sufficient interval between the application of the initiating carcinogen and the promoter, transformation occurs, and the ability of cells treated with subthreshold doses of DBA to form tumours is enhanced.

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Two-stage Malignant Transformation of Rat Fibroblasts in Tissue Culture

Cited by 92 publications

References 11 publications

Two-stage carcinogenesis with rat embryo cells in tissue culture

Two-stage carcinogenesis with rat embryo cells in tissue culture

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

Two-stage malignant transformation in hamster embryo cells

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