Dibutyltin and tributyltin compounds induce thymus atrophy in rats due to a selective action on thymic lymphoblasts.
Di-n-butyltin dichloride (DBTC) or tri-n-butyltin chloride (TBTC) given in the diets of rats have previously been shown to cause atrophy of the thymus and subsequently suppression of the T-cell-dependent immune responses. To study the mechanism of the immunotoxic effects, the dose-effect relationships and the kinetics of the thymus atrophy caused by DBTC and TBTC were investigated in detail. A single oral dose of DBTC or TBTC to rats induced a dose-related reduction of relative thymus weight, which was maximal 4 days after intubation. The log dose-effect relationships for both compounds were linear and ran parallel over a dose range of 5-60 mg/kg. Dose levels calculated to cause 50% reduction of relative thymus weight were 18 mg DBTC and 29 mg TBTC per kg body wt. A single oral dose of mono-n-butyltin trichloride (MBTC), however, did not cause thymus atrophy at dose levels up to 180 mg/kg. The kinetics of the dibutyltin- and tributyltin-induced thymus atrophy in rats were investigated by measuring thymus weight, total thymic cell count, number of small, intermediate and large cells and the incorporation of DNA, RNA and protein precursors into isolated thymocytes during a period of 9 days after a single oral dose. DBTC and TBTC caused atrophy of the thymus due to a selective reduction in the number of rapidly proliferating lymphoblasts in the first 2 days after dosing. As a consequence the large pool of small lymphocytes declined in the following 2 days. On the fourth day, when atrophy was most pronounced, the frequency of the lymphoblasts increased above the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Snoeij
N J
NJ
Veterinary Pharmacology, Pharmacy and Toxicology, University of Utrecht, The Netherlands.
Penninks
A H
AH
Seinen
W
W
D000284:Administration, Oral; D000818:Animals; D002452:Cell Count; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D008297:Male; D009929:Organ Size / Q000187:drug effects; D009947:Organotin Compounds / Q000008:administration & dosage / Q000633:toxicity*; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014220:Trialkyltin Compounds / Q000008:administration & dosage / Q000633:toxicity*
D009947:Organotin Compounds; D014220:Trialkyltin Compounds; C011559:tributyltin; D012313:RNA; D004247:DNA; C020735:dibutyldichlorotin