Effets de proliférateurs des peroxysomes hépatiques sur la transformation morphologique et la communication intercellulaire des cellules SHE et sur la coopération métabolique des cellules V79

Abstract : We evluated the capabilities of two in vitro assays to detect non-genotoxic carcinogens such as hepatic peroxisome proliferators (HPPs). The results showed that morphological transformation of the primary Syrian hamster embryo (SHE) cells is a valuable criterion. We studied the influence of the experimental conditions and the pH of the culture medium used on the transforming potencies of four HPPs (clofibrate, MCP, DEPH, MEHP). From this study, we concluded that : the sensitivity increased when the exposure to the tested HPP was renewed one or two times during the assay and when the medium used was at pH 7.0, the procedure based on sequential exposures of the cells to the tested HPP and either a model initiator or a model promoter can be advised since it enables to detect interactions between non-genotoxic carcinogens. The study of GJIC is also an interesting criterion for the in vitro detection of carcinogens. Indeed, the four HPPs we tested all had an inhibiting effect on GJIC both measured by dye transfer in SHE and V79 cells and by the evaluation of metabolic cooperation between V79 cells. Ours study also showed that exposure of the cells to HPPs does not affect the phosphorylation status of connexin 43 (Cx43), expressed in the cell systems. Except for MEHP, which lead to the disappearence of the immunofluorescent signal produced by Cx43 in SHE and V79 cells, the HPPs did not affect the cellular localization of Cx43. The effect of MEHP could be explained by epitopa masking due to conformational changes of Cx43 induced by the exposure of the cells to the HPP. We evaluated the effects of TPA on the same parameters and found thzt TPA strongly inhibited GJIC in the two systems. TPA modified the phosphorylation status of Cx43 in V79 cells but not in SHE cells and induced the disappearance of the immunofluorescent signal of connexin 43 in both systems. The absence of correlation between GJIC and the post-translationnal regulation of Cx43 could mean that other connexins than Cx43 may be involved in the GJIC of the cells we used. Our results show that both the transformation assay and the evaluation of intercellular communication are valuable tools to detect carcinogens
Document type :
Theses
Complete list of metadatas

Cited literature [175 references]  Display  Hide  Download

https://hal.univ-lorraine.fr/tel-01777193
Contributor : Administrateur Du Ccsd <>
Submitted on : Tuesday, April 24, 2018 - 4:13:59 PM
Last modification on : Thursday, April 26, 2018 - 1:28:16 AM
Long-term archiving on : Wednesday, September 19, 2018 - 3:36:44 PM

File

Cruciani.Veronique.SMZ9705.pdf
Files produced by the author(s)

Identifiers

  • HAL Id : tel-01777193, version 1

Collections

Citation

Véronique Cruciani. Effets de proliférateurs des peroxysomes hépatiques sur la transformation morphologique et la communication intercellulaire des cellules SHE et sur la coopération métabolique des cellules V79. Sciences agricoles. Université Paul Verlaine - Metz, 1997. Français. ⟨NNT : 1997METZ005S⟩. ⟨tel-01777193⟩

Share

Metrics

Record views

8

Files downloads

5