ISSN:
1432-1335
Schlagwort(e):
Chloroethylnitrosoureas
;
Alkaline elution
;
DNA-interstrand crosslinks
;
Myelosuppression
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Summary This study compares the level of DNA-DNA interstrand crosslinking in murine bone marrow with the decrease in mean number of blood progenitor cells in mice treatedwith chloroethylnitrosoureas. Male C57BL6 X C3HF1 mice were treated with single IP injections of 1-(2-chloroethyl)-1-nitroso-3-(methylene-carboxamido)-urea (acetamido-CNU), 1,2-bis(2-chloroethyl)-1-nitrosourea (BCNU), 2-[3-(2-chloroethyl)3-nitrosoureido]-β-d-glucopyranose (chlorozotocin), or 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea (HECNU). After 16h three aliquots of pooled bone marrow were assayed for DNA damage in the form of DNA-DNA interstrand crosslinks and myelosuppression in terms of the depletion of granulocyte-committed (CFU-C) and pluripotent (CFU-S) stem cell activity. Both acetamido-CNU and HECNU produced a dose-dependent increase in DNA-DNA insterstrand crosslinking, which was paralleled by a marked inhibition of both types of progenitor cells. BCNU and chlorozotocin, however, were much less effective at crosslinking DNA, and were much less myelosuppressive in terms of CFU-C and CFU-S activity. These data suggest a correlation between the degree of myelosuppression at the level of the stem cell and the extent of DNA damage in murine bone marrow. The levels of haematosuppression did not parallel the acute single-dose toxicity in mice but rather reflected the relative antileukaemic activity of these agents. However, the degree of recovery of the stem cell compartments may be more relevant to the clinically important long-term toxicity after single and repeated doses.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF00390986
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