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Low-temperature prevents side effects of an anti-cancer drug, cyclophosphamide, on organ development: a study of ex vivo organ culture model

ABSTRACT: Development of chemotherapy has led to a high survival rate of cancer patients; however, severe side effects of anti-cancer drugs, including organ hypoplasia, persists. This study examined the molecular mechanism of the side effects of cyclophosphamide (CPA), a commonly used anti-cancer drug for the treatment of leukemia, and determined how to suppress the side effects using an organ culture system. Treatment with CPA disturbed the growth of tooth germs by inducing apoptosis and suppressing cellular proliferation and differentiation. Furthermore, organs cultured at low-temperature could avoid the CPA-mediated inhibition of organ morphogenesis and differentiation. Cap analysis of gene expression of CPA-treated tooth germ revealed that the expression of genes related to the G1/S cell cycle checkpoint were down-regulated in the CPA-treated tooth germ cultured at low-temperature. In vitro analysis revealed that low-temperature impeded Rb phosphorylation and caused cell cycle arrest at the G1 phase. This can prevent the CPA-mediated cell damage of DNA replication caused by the cross-linking reaction of CPA. Our results revealed that the side effects of CPA on organ development can be avoided by maintaining a low temperature. Further, this study provides a new screening model for assessing the effects of anticancer drugs on organ development.

ORGANISM(S): Mus musculus

PROVIDER: GSE182499 | GEO | 2021/08/23

REPOSITORIES: GEO

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Low-temperature prevents side effects of an anti-cancer drug, cyclophosphamide, on organ development: a study of ex vivo organ culture model

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