Chemotherapeutic agents used in the treatment of childhood malignancies have direct effects on growth plate chondrocyte proliferation.

2.50
Hdl Handle:
http://hdl.handle.net/10541/92026
Title:
Chemotherapeutic agents used in the treatment of childhood malignancies have direct effects on growth plate chondrocyte proliferation.
Authors:
Robson, Helen; Anderson, Elizabeth; Eden, Tim O B; Isaksson, O; Shalet, Stephen M
Abstract:
Short stature is one of the most well recorded long term sequelae for adult survivors of childhood malignancies. It has become increasingly apparent that cytotoxic chemotherapy, as well as craniospinal irradiation, has a major impact on growth, but there are virtually no studies which explore the mechanisms by which these cytotoxic drugs affect growth. We have used an in vitro system to investigate the direct effects of a range of chemotherapeutic agents on the proliferative responses of rat tibial growth plate chondrocytes, both in suspension and monolayer culture. The glucocorticoids and purine anti-metabolites reduced chondrocyte proliferation both in monolayer and suspension cultures and this resulted from an increase in cell doubling times with a concomittant reduction in the numbers of S phase cells. DNA damaging agents (e.g. actinomycin-D) were also able to reduce chondrocyte proliferation, both in monolayer and suspension culture. This, however, was the result of a cell cycle arrest and subsequent cell death. In our studies, methotrexate had no significant effect on the proliferative responses of the chondrocytes either in monolayer or suspension culture. These results indicate direct effects of a range of chemotherapeutic agents on the proliferative responses of growth plate chondrocytes. Both cytostatic and cytotoxic effects were observed although the impact of either the potential loss of cells from the proliferative pool during chondrocyte differentiation, or the reduction in the rate of chondrocyte turnover on long bone growth remains to be elucidated.
Affiliation:
Christie Hospital NHS Trust, Manchester, UK.
Citation:
Chemotherapeutic agents used in the treatment of childhood malignancies have direct effects on growth plate chondrocyte proliferation. 1998, 157 (2):225-35 J. Endocrinol.
Journal:
Journal of Endocrinology
Issue Date:
May-1998
URI:
http://hdl.handle.net/10541/92026
PubMed ID:
9659285
Type:
Article
Language:
en
ISSN:
0022-0795
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.accessioned2010-02-12T15:48:11Z-
dc.date.available2010-02-12T15:48:11Z-
dc.date.issued1998-05-
dc.identifier.citationChemotherapeutic agents used in the treatment of childhood malignancies have direct effects on growth plate chondrocyte proliferation. 1998, 157 (2):225-35 J. Endocrinol.en
dc.identifier.issn0022-0795-
dc.identifier.pmid9659285-
dc.identifier.urihttp://hdl.handle.net/10541/92026-
dc.description.abstractShort stature is one of the most well recorded long term sequelae for adult survivors of childhood malignancies. It has become increasingly apparent that cytotoxic chemotherapy, as well as craniospinal irradiation, has a major impact on growth, but there are virtually no studies which explore the mechanisms by which these cytotoxic drugs affect growth. We have used an in vitro system to investigate the direct effects of a range of chemotherapeutic agents on the proliferative responses of rat tibial growth plate chondrocytes, both in suspension and monolayer culture. The glucocorticoids and purine anti-metabolites reduced chondrocyte proliferation both in monolayer and suspension cultures and this resulted from an increase in cell doubling times with a concomittant reduction in the numbers of S phase cells. DNA damaging agents (e.g. actinomycin-D) were also able to reduce chondrocyte proliferation, both in monolayer and suspension culture. This, however, was the result of a cell cycle arrest and subsequent cell death. In our studies, methotrexate had no significant effect on the proliferative responses of the chondrocytes either in monolayer or suspension culture. These results indicate direct effects of a range of chemotherapeutic agents on the proliferative responses of growth plate chondrocytes. Both cytostatic and cytotoxic effects were observed although the impact of either the potential loss of cells from the proliferative pool during chondrocyte differentiation, or the reduction in the rate of chondrocyte turnover on long bone growth remains to be elucidated.en
dc.language.isoenen
dc.subject.mesh6-Mercaptopurine-
dc.subject.meshAnimals-
dc.subject.meshAntibiotics, Antineoplastic-
dc.subject.meshAntimetabolites, Antineoplastic-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshCarboplatin-
dc.subject.meshCell Cycle-
dc.subject.meshCell Division-
dc.subject.meshCells, Cultured-
dc.subject.meshChondrocytes-
dc.subject.meshCisplatin-
dc.subject.meshDactinomycin-
dc.subject.meshDexamethasone-
dc.subject.meshEtoposide-
dc.subject.meshGrowth Plate-
dc.subject.meshMale-
dc.subject.meshMethotrexate-
dc.subject.meshPrednisolone-
dc.subject.meshRats-
dc.subject.meshRats, Sprague-Dawley-
dc.subject.meshThioguanine-
dc.titleChemotherapeutic agents used in the treatment of childhood malignancies have direct effects on growth plate chondrocyte proliferation.en
dc.typeArticleen
dc.contributor.departmentChristie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalJournal of Endocrinologyen
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