DRUG SEQUENCE-DEPENDENT TOXICITY AND SMALL BOWEL MUCOSAL INJURY IN MICE TREATED WITH LOW-DOSES OF 3-DEAZAURIDINE AND 1-BETA-D-ARABINOFURANOSYLCYTOSINE

  • 1 January 1979
    • journal article
    • research article
    • Vol. 39  (6) , 2216-2219
Abstract
The toxicity to mice of combinations of 1-.beta.-D-arabinofuranosylcytosine [ara-C] and 3-deazauridine was investigated. The drugs were administered daily i.p. on days 1-5, each drug at 10 mg/kg body wt; 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 2-8 h prior to ara-C; most mice treated in this way died within 3 days of the last treatment. Histological examination showed 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. Treatments with this drug combination at the same dosages were tolerated when the 2 agents were administered simultaneously or when ara-C 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 ara-C component was preceded by treatment with nitrobenzylthioinosine (100 mg/kg), a potent inhibitor of nucleoside transport.