Molecular machinery underlying tissue-specific development of adverse drug reactions induced by anticancer drugs

本研究的目的是阐明5-氟尿嘧啶（5-FU）诱导的骨髓毒性是否是氧化应激的原因，并证明参与组织特异性药物不良反应发展的机制。5-FU诱导的小鼠骨髓毒性与细胞内谷胱甘肽和Nrf 2活性直接相关，表明氧化应激参与了该过程。此外，5-FU在骨髓和移植瘤中诱导不同的p53反应，这可能参与了5-FU毒性的组织选择性。

The purpose of this study was to clarify whether 5-fluorouracil (5-FU)-induced myelotoxicity is a cause of oxidative stress and to demonstrate machineryinvolved in tissue-specific development of adverse-drug reactions. 5-FU-inducedmyelotoxicity in mice was directly linked to intracellular glutathione and activity of Nrf2,indicating that oxidative stress is involved in the process. In addition, 5-FU induced different responses of p53 in the bone marrow and tumor xenografts, which could be participated in the tissue selectivity of the 5-FU-mediated toxicity.