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Analysis of micronuclei and DNA single-strand breaks in mouse splenocytes and peripheral lymphocytes after oral administration of tetramethylthiuram disulfide (thiram)

TitoloAnalysis of micronuclei and DNA single-strand breaks in mouse splenocytes and peripheral lymphocytes after oral administration of tetramethylthiuram disulfide (thiram)
Tipo di pubblicazioneArticolo su Rivista peer-reviewed
Anno di Pubblicazione1998
AutoriVillani, Paola, Andreoli C., Crebelli R., Pacchierotti Francesca, Zijno A., and Carere A.
RivistaFood and Chemical Toxicology
Volume36
Paginazione155-164
ISSN02786915
Parole chiaveAdministration, animal cell, Animalia, Animals, article, Cell Division, Cells, Chromosome aberration, Cultured, DNA, DNA damage, DNA strand breakage, Fungicides, Industrial, lymphocyte, male, Mice, micronucleus, Micronucleus Tests, mouse, mutagenicity, Mutagenicity Tests, nonhuman, Oral, Single-Stranded, Spleen, spleen cell, T-Lymphocytes, thiram
Abstract

The fungicide thiram (tetramethylthiuram disulfide, TMTD) was administered by repeated oral intubations to groups of male B6C3F1 mice at 100, 300 and 900 mg/kg body weight for 4 consecutive days, or at 300 mg/kg for 8 and 12 days. 24 hr after the last treatment animals were killed, and splenocyte cultures were set up for the analysis of micronuclei by the cytokinesis-block method. DNA single strand breaks (ssb) and alkali labile sites were also analysed by the single cell gel electrophoresis (Comet) assay in splenocytes and lymphocytes of animals receiving the 8- and 12-day treatments. Parallel experiments with human peripheral lymphocytes were carried out to assess the ability of thiram to induce micronuclei and DNA ssb and alkaline labile sites under in vitro conditions. No significant increase of micronucleated splenocytes was observed in treated animals, despite some evidence of treatment-related cellular toxicity. A borderline excess of DNA damage was suggested by the Comet assay on circulating lymphocytes, whereas negative results were obtained with splenocytes. In vitro, positive results with both genetic end points were obtained in assays with human lymphocytes in the dose ranges 0.5-24 μg/ml and 0.1-8 μg/ml for micronucleus and Comet assays, respectively. TheSe results suggest that thiram, despite its established genotoxicity in vitro, is devoid of appreciable clastogenic and/or aneugenic activity in vivo after oral administration to mice at the maximum tolerated dose.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-0032549450&doi=10.1016%2fS0278-6915%2897%2900147-6&partnerID=40&md5=aefdf4bf72a0a19d427f631ee6f12124
DOI10.1016/S0278-6915(97)00147-6
Citation KeyVillani1998155