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

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    Authors
    Robson, Helen
    Anderson, Elizabeth
    Eden, Tim O B
    Isaksson, O
    Shalet, Stephen M
    Affiliation
    Christie Hospital NHS Trust, Manchester, UK.
    Issue Date
    1998-05
    
    Metadata
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    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.
    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
    URI
    http://hdl.handle.net/10541/92026
    PubMed ID
    9659285
    Type
    Article
    Language
    en
    ISSN
    0022-0795
    Collections
    All Christie Publications
    All Paterson Institute for Cancer Research

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