Abstract
Cyclophosphamide (CP) and mafosfamide (MF) are converted in various tissues to 4-hydroxycyclophosphamide, and subsequently to aldophosphamide (AP). In target cells, AP is further broken down to the toxic compounds phosphoramide mustard and acrolein. AP can be oxidized to a nontoxic metabolite (carboxyphosphamide) catalyzed by one or more types of aldehyde dehydrogenase (ALDH) isoenzymes. Thus, intracellular ALDH activity appears to be an important determinant in modulating sensitivity to CP in patients undergoing chemotherapy. The class 1 cytosolic enzyme (ALDH1) has been shown to be particularly important in the metabolism of CP and MF derivatives in bone marrow cells (Kohn and Sladek, 1985; Kastan et al., 1990; Dockham et al., 1992). The overall contribution of blood ALDH in this respect is, however, not known. In the present study, we have determined ALDH activity in human blood subfractions from healthy subjects and malignant lymphoma patients undergoing combination chemotherapy plus or minus CP.
This work will be a part of the MD thesis of M. Metzenthin to be submitted to the Faculty of Medicine, University of Hamburg.
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Metzenthin, M., Meier-Tackmann, D., Agarwal, D.P., Zschaber, R., Weh, HJ. (1996). Aldehyde Dehydrogenase-Mediated Metabolism of Acetaldehyde and Mafosfamide in Blood of Healthy Subjects and Patients with Malignant Lymphoma. In: Weiner, H., Lindahl, R., Crabb, D.W., Flynn, T.G. (eds) Enzymology and Molecular Biology of Carbonyl Metabolism 6. Advances in Experimental Medicine and Biology, vol 414. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5871-2_17
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DOI: https://doi.org/10.1007/978-1-4615-5871-2_17
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