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Alkaline DNA fragmentation,DNA disentanglement evaluated viscosimetrically and sister chromatid exchanges,after treatment in vivo with nitrofurantoin
Authors:Silvio Parodi  Mauro Pala  Patrizia Russo  Cecilia Balbi  Maria Luisa Abelmoschi  Maurizio Taningher  Annalisa Zunino  Laura Ottaggio  Marcella de Ferrari  Antonino Carbone  Leonardo Santi
Institution:1. Department of Oncology, University of Genoa, I-16132 Genoa Italy;2. Istituto Scientifico per lo Studio e la Cura dei Tumori-Istituto Nazionale per la Ricerca sul Cancro, I-16132 Genoa Italy
Abstract:Nitrofurantoin was not positive as a carcinogen in long term assays. In vitro it was positive in some short term tests and negative in others. We have examined Nitrofurantoin for its capability of inducing DNA damage in vivo. With the alkaline elution technique, Nitrofurantoin appeared clearly positive in all the tissues examined (liver, kidney, lung, spleen and bone marrow). In the liver we also observed some cross-linking effect. In bone marrow cells Nitrofurantoin was also clearly positive in terms of sister chromatid exchanges (SCEs) induction. DNA damage in vivo was also examined with a viscosimetric method, more sensitive than alkaline elution. With this method the results were essentially negative, suggesting that the two methods detect different types of damage. In view of its positivity in many organs and in two short term tests in vivo, the carcinogenic potential of Nitrofurantoin should be reconsidered.
Keywords:Nitrofurantoin - DNA damage - Sister chromatid exchanges - Viscosimetry - Alkaline elution  BSA  bovine serum albumin  BUdR  5-bromodeoxyuridine  DABA  3  5-diaminobenzoic acid dihydrochloride  DMEM  Dulbecco's modified Eagle medium  DMS  dimethylsulphate  EGTA  FCS  fetal calf serum  human foreskin fibroblasts  (ethylenedinitrilo)-tetraacetic acid  NF  nitrofurantoin  PBS  phosphate buffered saline  PPLO  pleuro-pneumonial-like organism  SCE  sister chromatid exchange  TCA  trichloroacetic acid  TEA-OH  tetraethyl ammonium hydroxide
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