Comparative tissue distribution and excretion of orally administered [3H]diacetoxyscirpenol (anguidine) in rats and mice.
A quantitative comparison of tissue distribution and excretion of an orally administered sublethal dose of [3H]diacetoxyscirpenol (anguidine) was made in rats and mice 90 min, 24 hr, and 7 days after treatment. Total recoveries of 95-100% were obtained. Approximately 90% of the dose was excreted in urine and feces during the first 24 hr with a feces:urine ratio of about 1:4.5 in both species. Carcass and tissue radioactivity dropped rapidly during the first 24 hr but remained relatively constant at low, but detectable, levels (1.5-3.5% of dose) over the course of the experiment. Few substantive interspecies differences were noted in tissue distribution. At 90 min the highest percentage of dose was in tissues involved in sequestering diacetoxyscirpenol because of high body water/lipid content (carcass, skin) or the absorption (stomach, small intestine), metabolism (liver), or excretion (kidney) of the toxin. The rank order of these tissues was generally stable over the course of the experiment. When data were expressed as specific radioactivity (dpm/g tissue) instead, the carcass and skin dropped from the top rank tissues at 90 min and were replaced by the spleen and cecum. At 24 hr and 7 days the top-ranked order of tissues shifted to include organs associated with trichothecene-induced toxicity such as the lymphohematopoietic system (spleen, thymus, and femur bone marrow), heart, and testis (in mouse) as well as the cecum and large intestine. In addition, the rate of loss of radioactivity with time generally did not decrease as rapidly in these target organs as observed in liver, kidney, skin, and carcass. Brain radioactivity, though very low, also diminished relatively slowly. Significant differences in specific radioactivity which did occur between the rat and mouse tended to occur in target organs and with the higher levels present in the mouse. These data were discussed in terms of interspecies differences in lethality and target organ toxicity.
Wang
J S
JS
Division of Toxicology, Whitaker College of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139.
Busby
W F
WF
Wogan
G N
GN
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D005243:Feces / Q000032:analysis; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011919:Rats, Inbred Strains; D012717:Sesquiterpenes / Q000493:pharmacokinetics*; D013997:Time Factors; D014018:Tissue Distribution; D014255:Trichothecenes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D014316:Tritium
D000970:Antineoplastic Agents; D012717:Sesquiterpenes; D014255:Trichothecenes; D014316:Tritium; C001809:diacetoxyscirpenol