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Mutagenicity of N-ethyl-N-nitrosourea, N-methyl-N-nitrosourea, methyl methanesulfonate and ethyl methanesulfonate in the developing Syrian hamster fetus

  1. Author:
    Donovan, P.
    Smith, G.

  2. Author Address

    [Donovan, Paul; Smith, George] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA.;Donovan, P, NCI, Comparat Carcinogenesis Lab, Bldg 538,Room 205 NCI Frederick, Frederick, MD 21702 USA.;donovanp@mail.nih.gov
    1. Year: 2010
    2. Date: Jun
  2. Journal: Mutation Research-Genetic Toxicology and Environmental Mutagenesis
    1. 699
    2. 1-2
    3. Pages: 55-57
  4. Type of Article: Article
  5. ISSN: 1383-5718
  1. Abstract:

    N-ethyl-N-nitrosourea (ENU) and N-methyl-N-nitrosourea (MNU) are well-known direct-acting transplacental mutagens and carcinogens. Methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) are also direct-acting but more stable compounds and form a different proportion of the various methyl and ethyl DNA adducts. The transplacental mutagenicity and carcinogenicity of MMS and EMS have not been well characterized. We tested the mutagenicity to the developing Syrian hamster by these compounds under identical conditions and with a range of dose. Mutant fetal cells were selected for diphtheria toxin resistance. All four compounds were significantly mutagenic. MNU was the most active and MMS the least active of the compounds. ENU and MNU demonstrated linear dose-response curves, whereas that for EMS seemed to be supralinear over the range 0.125-0.5 mmol/kg. At its highest dose, EMS was comparable to ENU in mutagenicity. In view of a recent accidental exposure of pregnant women and others to EMS, further studies of this compound in animal models may be warranted. Published by Elsevier B.V.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.mrgentox.2010.03.012
  3. View record in Web of Science®
  4. WOS: 000279528700010

Library Notes

  1. Fiscal Year: FY2009-2010
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