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Genetic effects of dimethyl sulfate, diethyl sulfate, and related compounds
Abstract:
DMS and DES are monofunctional alkylating agents that have been shown to induce mutations, chromosomal aberrations, and other genetic alterations in a diversity of organisms. They have also been shown to be carcinogenic in animals. As an alkylating agent, DMS is a typical SN2 agent, attacking predominantly nitrogen sites in nucleic acids. DES is capable of SN1 alkylations as well as SN2 and thereby causes some alkylation on oxygen sites including the O6-position of guanine which is thought to be significant in mutagenesis by direct mispairing. The mutagenicity of DMS is better explained in terms of indirect, repair-dependent processes. With respect to both alkylating activity and genetic effects, striking similarities are found between DMS and MMS and between DES and EMS. In most systems where they have been tested, both DMS and DES are mutagenic. Results of many of the mutagenesis studies involving these compounds and other alkylating sulfuric acid esters are summarized in Tables 6, 7, 8, 9 and 10 of this review. Most data are consistent with these agents acting primarily as base-pair substitution mutagens. In the case of DES, strong specificity for G.C to A.T transitions has been reported in some systems but has not been clearly supported in some others. Low levels of frameshift mutations of the deletion type are also likely. In addition to the induction of mutations, recombinogenic and clastogenic effects have been described.
Insights
Dimethyl sulfate (DMS) and diethyl sulfate (DES) are potent mutagens and carcinogens. These alkylating agents induce genetic alterations through various mechanisms, primarily base-pair substitutions.
Area of Science:
- Chemical Mutagenesis
- Genotoxicology
- Molecular Biology
Background:
- Dimethyl sulfate (DMS) and diethyl sulfate (DES) are monofunctional alkylating agents.
- These agents are known to induce mutations, chromosomal aberrations, and exhibit carcinogenicity in animal models.
- DMS acts as an SN2 agent, primarily alkylating nitrogen sites in nucleic acids.
Purpose of the Study:
- To review and summarize the mutagenic and genetic effects of DMS and DES.
- To elucidate the mechanisms of mutagenesis induced by these alkylating agents.
- To compare the genetic activities of DMS and DES with related compounds like MMS and EMS.
Main Methods:
- Review of existing mutagenesis studies involving DMS and DES.
- Analysis of data on genetic alterations, including mutations and chromosomal aberrations.
- Comparison of alkylating activity and genetic effects across different organisms and experimental systems.
Main Results:
- Both DMS and DES are mutagenic across various test systems.
- DMS-induced mutagenicity is often linked to indirect, repair-dependent processes.
- DES can induce SN1 and SN2 alkylations, potentially alkylating oxygen sites like guanine's O6 position, contributing to mispairing.
- The primary mutagenic effect appears to be base-pair substitutions, with some evidence for G:C to A:T transitions and deletion-type frameshift mutations.
Conclusions:
- DMS and DES are significant genotoxic agents with mutagenic and clastogenic properties.
- Similarities in genetic effects exist between DMS and MMS, and between DES and EMS.
- The mechanisms of mutagenesis involve both direct DNA alkylation and indirect, repair-mediated pathways, with base-pair substitutions being a major outcome.
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