Differential influence of TGFbeta1 and TGFbeta3 isoforms on cell cycle kinetics and postirradiation recovery of normal and malignant colorectal epithelial cells.

2.50
Hdl Handle:
http://hdl.handle.net/10541/94871
Title:
Differential influence of TGFbeta1 and TGFbeta3 isoforms on cell cycle kinetics and postirradiation recovery of normal and malignant colorectal epithelial cells.
Authors:
Robson, Helen; Spence, Katherine; Anderson, Elizabeth; Potten, Christopher S; Hendry, Jolyon H
Abstract:
PURPOSE: A clonogenic assay was used to determine the effects of the growth factors TGFbeta1 and TGFbeta3 on the radiation responses of a normal rat epithelial cell line (IEC6) and a human colonic carcinoma epithelial cell line (Widr). METHODS AND MATERIALS: The radiation sensitivity and ability to recover from potentially lethal damage (PLD), of preconfluent monolayer cultures, was assessed in the presence of the growth factors for 24 h prior to, during, and after irradiation. RESULTS: The surviving fractions of both cell lines assessed immediately following irradiation were unaffected by TGFbeta1 or TGFbeta3. However, TGFbeta3 (but not TGFbeta1) significantly reduced the amount of PLD recovery in the Widr cells (but not in the IEC6 cells). This was associated with a reduction in the shoulder region of the survival curve, rather than a change in slope. A comparative analysis of the effects of TGFbetas 1 and 3 on cell cycle events in the two cell lines demonstrated significantly more Widr cells in the S phase, in the presence of TGFbeta3 only, compared to the controls. This remained constant both before and immediately following irradiation. In the IEC6 cell line TGFbeta3 produced an increase in the numbers of G1 phase cells, characteristic of a G1 arrest. CONCLUSION: It seems likely that TGFbeta3-induced radiosensitisation in Widr cells, 6 h after a single dose of irradiation, is related to its effects on cell cycle events such that the failure of these cells to arrest in G1, either before or after irradiation, results in significantly reduced recovery from DNA damage. This, however, may not be the only mechanism by which this growth factor produces this effect. Indeed, it will also be necessary to investigate these effects in in vivo models and to determine the response to fractionated irradiation before the potential therapeutic benefit of both the differential effects observed between the two TGFbeta isoforms and also between the malignant and normal cell lines can be fully assessed.
Affiliation:
Tumour Biochemistry Department, Christie Hospital NHS Trust, CRC Departments, Withington, UK.
Citation:
Differential influence of TGFbeta1 and TGFbeta3 isoforms on cell cycle kinetics and postirradiation recovery of normal and malignant colorectal epithelial cells. 1997, 38 (1):183-90 Int. J. Radiat. Oncol. Biol. Phys.
Journal:
International Journal of Radiation Oncology, Biology, Physics
Issue Date:
1-Apr-1997
URI:
http://hdl.handle.net/10541/94871
DOI:
10.1016/S0360-3016(97)00248-4
PubMed ID:
9212022
Type:
Article
Language:
en
ISSN:
0360-3016
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorRobson, Helenen
dc.contributor.authorSpence, Katherineen
dc.contributor.authorAnderson, Elizabethen
dc.contributor.authorPotten, Christopher Sen
dc.contributor.authorHendry, Jolyon Hen
dc.date.accessioned2010-03-24T14:36:40Z-
dc.date.available2010-03-24T14:36:40Z-
dc.date.issued1997-04-01-
dc.identifier.citationDifferential influence of TGFbeta1 and TGFbeta3 isoforms on cell cycle kinetics and postirradiation recovery of normal and malignant colorectal epithelial cells. 1997, 38 (1):183-90 Int. J. Radiat. Oncol. Biol. Phys.en
dc.identifier.issn0360-3016-
dc.identifier.pmid9212022-
dc.identifier.doi10.1016/S0360-3016(97)00248-4-
dc.identifier.urihttp://hdl.handle.net/10541/94871-
dc.description.abstractPURPOSE: A clonogenic assay was used to determine the effects of the growth factors TGFbeta1 and TGFbeta3 on the radiation responses of a normal rat epithelial cell line (IEC6) and a human colonic carcinoma epithelial cell line (Widr). METHODS AND MATERIALS: The radiation sensitivity and ability to recover from potentially lethal damage (PLD), of preconfluent monolayer cultures, was assessed in the presence of the growth factors for 24 h prior to, during, and after irradiation. RESULTS: The surviving fractions of both cell lines assessed immediately following irradiation were unaffected by TGFbeta1 or TGFbeta3. However, TGFbeta3 (but not TGFbeta1) significantly reduced the amount of PLD recovery in the Widr cells (but not in the IEC6 cells). This was associated with a reduction in the shoulder region of the survival curve, rather than a change in slope. A comparative analysis of the effects of TGFbetas 1 and 3 on cell cycle events in the two cell lines demonstrated significantly more Widr cells in the S phase, in the presence of TGFbeta3 only, compared to the controls. This remained constant both before and immediately following irradiation. In the IEC6 cell line TGFbeta3 produced an increase in the numbers of G1 phase cells, characteristic of a G1 arrest. CONCLUSION: It seems likely that TGFbeta3-induced radiosensitisation in Widr cells, 6 h after a single dose of irradiation, is related to its effects on cell cycle events such that the failure of these cells to arrest in G1, either before or after irradiation, results in significantly reduced recovery from DNA damage. This, however, may not be the only mechanism by which this growth factor produces this effect. Indeed, it will also be necessary to investigate these effects in in vivo models and to determine the response to fractionated irradiation before the potential therapeutic benefit of both the differential effects observed between the two TGFbeta isoforms and also between the malignant and normal cell lines can be fully assessed.en
dc.language.isoenen
dc.subjectTumour Stem Cell Assayen
dc.subjectCultured Tumour Cellsen
dc.subject.meshAnimals-
dc.subject.meshCell Cycle-
dc.subject.meshCell Division-
dc.subject.meshCell Line-
dc.subject.meshCell Survival-
dc.subject.meshHumans-
dc.subject.meshRadiation Tolerance-
dc.subject.meshRats-
dc.subject.meshTransforming Growth Factor beta-
dc.subject.meshTumor Cells, Cultured-
dc.subject.meshTumor Stem Cell Assay-
dc.titleDifferential influence of TGFbeta1 and TGFbeta3 isoforms on cell cycle kinetics and postirradiation recovery of normal and malignant colorectal epithelial cells.en
dc.typeArticleen
dc.contributor.departmentTumour Biochemistry Department, Christie Hospital NHS Trust, CRC Departments, Withington, UK.en
dc.identifier.journalInternational Journal of Radiation Oncology, Biology, Physicsen
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