Two mechanisms of antimutagenicity of the aminothiols cysteamine and WR-1065 in Saccharomycescerevisiae

Toxicology in Vitro : an International Journal Published in Association with BIBRA
G R HoffmannP D McMaster

Abstract

The aminothiols cysteamine (CSM) and 2-[(aminopropyl)amino] ethanethiol (WR-1065) are radioprotectors, in that they reduce the mutagenic and potentially lethal consequences of ionizing radiation. We have studied the effects of these compounds on the induction of gene conversion at the trp5 locus in Saccharomyces cerevisiae strain D7 by two chemical mutagens: bleomycin (BLM) and beta-propiolactone (beta-PL). Both mutagens are potent recombinagens in this assay, giving rise to trp5 convertant frequencies greater than 10(-3). CSM and WR-1065 are effective antimutagens, reducing the recombinagenic effect of beta-PL by about 95%. The maximum reduction in the recombinagenic activity of BLM was 91% with CSM and 89% with WR-1065. Although the antimutagenic effects of the aminothiols against beta-PL and BLM appear to be similar, they stem from different underlying mechanisms. Aminothiols protect against the recombinagenicity of beta-PL through direct inactivation of the electrophilic mutagen by the nucleophilic antimutagen. They protect against that of BLM through modification of physiological conditions, most notably by depletion of oxygen required for BLM activity.

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Citations

Oct 22, 2002·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·K KaurA Nagpal
Jul 9, 2013·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Laura Vicedo JacociunasRafael Rodrigues Dihl
Mar 26, 2008·Regulatory Toxicology and Pharmacology : RTP·Ute UkelisStefan O Mueller
Jun 7, 2013·Environmental and Molecular Mutagenesis·George R HoffmannJason P Tartaglione
May 17, 2013·Environmental and Molecular Mutagenesis·Pamela L HeardMaik J Schuler
Sep 15, 2010·Environmental and Molecular Mutagenesis·George R HoffmannJason P Tartaglione
Oct 16, 2004·Expert Review of Anti-infective Therapy·Douglas N Fish
Jun 26, 2020·Skin Research and Technology : Official Journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI)·Maryam KarrabiMohammad Sahebkar

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