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The level of DNA interstrand crosslinking in bone marrow parallels the extent of myelosuppression in mice treated with four chloroethylnitrosoureas.

Abstract：

: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 treated with 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]-beta-D-glucopyranose (chlorozotocin), or 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea (HECNU). After 16 h 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 interstrand 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.

journal_name

J Cancer Res Clin Oncol

journal_title

Journal of cancer research and clinical oncology

authors

Bedford P,Berger MR,Eisenbrand G,Schmähl D

doi

10.1007/BF00390986

subject

Has Abstract

pub_date

1984-01-01 00:00:00

pages

141-7

issue

1

eissn

0171-5216

issn

1432-1335

journal_volume

108

pub_type

杂志文章

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