Abstract：
:The toxicity to mice of combinations of 1-beta-D-arabinofuranosylcytosine and 3-deazauridine was investigated. The drugs were administered daily i.p. on Days 1 to 5, each drug at 10 mg/kg body weight; these dosages are small fractions of the dosages at which 10% of the treated animals died when either drug was administered alone on the foregoing schedule. This drug combination was severely toxic when 3-deazauridine was administered 2 to 8 hr prior to 1-beta-D-arabinofuranosylcytosine; most mice treated in this way died within 3 days of the last treatment. Histological examination showed that severe damage to the small bowel mucosa resulted from treatment with the drugs in the above, lethal sequence. In contrast, treatments with this drug combination at the same dosages were tolerated when the two agents were administered simultaneously or when 1-beta-D-arabinofuranosylcytosine preceded 3-deazauridine. Under the latter conditions, small bowel mucosal injury was much less severe. Female mice were more sensitive to the toxic treatment regimen than were male mice and were protected against the latter when either the 3-deazauridine or the 1-beta-D-arabinofuranosylcytosine component was preceded by treatment with nitrobenzylthioinosine (100 mg/kg), a potent inhibitor of nucleoside transport.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Paterson AR,Jakobs ES,Lauzon GJ,Weinstein WMsubject
Has Abstractpub_date
1979-06-01 00:00:00pages
2216-9issue
6 Pt 1eissn
0008-5472issn
1538-7445journal_volume
39pub_type
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