Abstract：
:The acute intraperitoneal toxicities of chlorambucil and chlorambucil-spermidine conjugate have been compared, in mice. Both compounds were neurotoxic and also caused a prolonged fall in bodyweight and a depletion of lymphocyte numbers associated with a fall in the total leukocyte count and loss of spleen and thymus weight. Alanine aminotransferase and aspartate aminotransferase activities and blood urea nitrogen concentration were increased at 24 h after conjugate administration, but had returned to normal at 72 h. Chlorambucil significantly decreased blood urea nitrogen concentration for 72 h, but did not affect transferase activity. Tissue concentrations of conjugate were measurable in liver and kidney for 12 days and lung for 5 days after dosing. The toxicity of both compounds was cumulative. In mol/kg, the chlorambucil-spermidine conjugate was 10-fold more toxic than chlorambucil, on the basis of their neurotoxicity, but only 2- to 3-fold more toxic on the basis of their effects on lymphocyte depression. The increased toxicity of the conjugate does not improve its therapeutic index relative to chlorambucil.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Verschoyle RD,Carthew P,Holley JL,Cullis P,Cohen GMdoi
10.1016/0304-3835(94)90278-xsubject
Has Abstractpub_date
1994-10-14 00:00:00pages
217-22issue
2eissn
0304-3835issn
1872-7980pii
0304-3835(94)90278-Xjournal_volume
85pub_type
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