Glucocorticoid pretreatment reduces the cytotoxic effects of a variety of DNA-damaging agents on rat tibial growth-plate chondrocytes in vitro.

2.50
Hdl Handle:
http://hdl.handle.net/10541/92027
Title:
Glucocorticoid pretreatment reduces the cytotoxic effects of a variety of DNA-damaging agents on rat tibial growth-plate chondrocytes in vitro.
Authors:
Robson, Helen; Anderson, Elizabeth; Eden, Tim O B; Isaksson, O; Shalet, Stephen M
Abstract:
It is apparent that cytotoxic chemotherapy used to treat childhood malignancies has a major impact on subsequent growth. Our initial studies have demonstrated a direct adverse effect of individual glucocorticoids and cytotoxic agents on the proliferative capacity of rat tibial growth-plate chondrocytes in vitro. In the present study we investigated the interaction between these classes of agents using in vitro cultures of chondrocytes and examined the potential of these cells to recover from the adverse effects of the drugs as applied either alone or in combination. The glucocorticoids prednisolone and dexamethasone significantly reduced the growth rate of chondrocytes when present in cultures for 3 days. The growth rate increased following the removal of prednisolone and dexamethasone from cultures and reached 83.9+/-0.8% and 62.4+/-4.0%, respectively, of the control values after 11 days of culture. In contrast, cell numbers were significantly reduced when the DNA-damaging agents cisplatin, carboplatin, etoposide or actinomycin-D were present in cultures for 3 days. Very little recovery of cell growth was observed after removal of the drugs from cultures, with cell loss occurring in the cisplatin- and actinomycin-D-treated cultures. However, pretreatment of chondrocytes with either of the glucocorticoids completely ameliorated the cytotoxic effects of etoposide and carboplatin and significantly reduced those of cisplatin and actinomycin-D. Recovery of the cells treated with a combination of glucocorticoid and DNA-damaging agent was demonstrated by a significant increase in their ability to form colonies in suspension culture. Colony numbers were increased by a factor of between 5 and 80 as compared with the cells receiving medium alone followed by DNA-damaging agent. The glucocorticoids offer a protective effect in terms of the reduced cytotoxicity of DNA-damaging agents and improve the subsequent clonogenicity and recovery of growth-plate chondrocytes. This has important implications for treatment schedules involving both cytotoxic agents and glucocorticoids in childhood malignancies.
Affiliation:
Clinical Research Department, Christie Hospital NHS Trust, Manchester, UK.
Citation:
Glucocorticoid pretreatment reduces the cytotoxic effects of a variety of DNA-damaging agents on rat tibial growth-plate chondrocytes in vitro. 1998, 42 (2):171-6 Cancer Chemother. Pharmacol.
Journal:
Cancer Chemotherapy and Pharmacology
Issue Date:
1998
URI:
http://hdl.handle.net/10541/92027
DOI:
10.1007/s002800050802
PubMed ID:
9654119
Type:
Article
Language:
en
ISSN:
0344-5704
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorRobson, Helenen
dc.contributor.authorAnderson, Elizabethen
dc.contributor.authorEden, Tim O Ben
dc.contributor.authorIsaksson, Oen
dc.contributor.authorShalet, Stephen Men
dc.date.accessioned2010-02-12T15:48:45Z-
dc.date.available2010-02-12T15:48:45Z-
dc.date.issued1998-
dc.identifier.citationGlucocorticoid pretreatment reduces the cytotoxic effects of a variety of DNA-damaging agents on rat tibial growth-plate chondrocytes in vitro. 1998, 42 (2):171-6 Cancer Chemother. Pharmacol.en
dc.identifier.issn0344-5704-
dc.identifier.pmid9654119-
dc.identifier.doi10.1007/s002800050802-
dc.identifier.urihttp://hdl.handle.net/10541/92027-
dc.description.abstractIt is apparent that cytotoxic chemotherapy used to treat childhood malignancies has a major impact on subsequent growth. Our initial studies have demonstrated a direct adverse effect of individual glucocorticoids and cytotoxic agents on the proliferative capacity of rat tibial growth-plate chondrocytes in vitro. In the present study we investigated the interaction between these classes of agents using in vitro cultures of chondrocytes and examined the potential of these cells to recover from the adverse effects of the drugs as applied either alone or in combination. The glucocorticoids prednisolone and dexamethasone significantly reduced the growth rate of chondrocytes when present in cultures for 3 days. The growth rate increased following the removal of prednisolone and dexamethasone from cultures and reached 83.9+/-0.8% and 62.4+/-4.0%, respectively, of the control values after 11 days of culture. In contrast, cell numbers were significantly reduced when the DNA-damaging agents cisplatin, carboplatin, etoposide or actinomycin-D were present in cultures for 3 days. Very little recovery of cell growth was observed after removal of the drugs from cultures, with cell loss occurring in the cisplatin- and actinomycin-D-treated cultures. However, pretreatment of chondrocytes with either of the glucocorticoids completely ameliorated the cytotoxic effects of etoposide and carboplatin and significantly reduced those of cisplatin and actinomycin-D. Recovery of the cells treated with a combination of glucocorticoid and DNA-damaging agent was demonstrated by a significant increase in their ability to form colonies in suspension culture. Colony numbers were increased by a factor of between 5 and 80 as compared with the cells receiving medium alone followed by DNA-damaging agent. The glucocorticoids offer a protective effect in terms of the reduced cytotoxicity of DNA-damaging agents and improve the subsequent clonogenicity and recovery of growth-plate chondrocytes. This has important implications for treatment schedules involving both cytotoxic agents and glucocorticoids in childhood malignancies.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshAnti-Inflammatory Agents-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshCarboplatin-
dc.subject.meshCell Division-
dc.subject.meshChondrocytes-
dc.subject.meshCisplatin-
dc.subject.meshDactinomycin-
dc.subject.meshDexamethasone-
dc.subject.meshDrug Interactions-
dc.subject.meshEtoposide-
dc.subject.meshFemale-
dc.subject.meshMale-
dc.subject.meshPrednisolone-
dc.subject.meshRats-
dc.subject.meshTibia-
dc.titleGlucocorticoid pretreatment reduces the cytotoxic effects of a variety of DNA-damaging agents on rat tibial growth-plate chondrocytes in vitro.en
dc.typeArticleen
dc.contributor.departmentClinical Research Department, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalCancer Chemotherapy and Pharmacologyen

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.