The reaction of nucleic acids with mustard gas

Elmore, D. T.; Gulland, John Masson; Jordan, D. O.; Taylor, H. F. W.

doi:10.1042/bj0420308

Cited by 59 publications

(6 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In parallel to the structural studies with enzymes, chemical reagents that are able to interact or modify nucleic acids were also investigated, in order to understand the properties of RNA. Historically, one of the first chemicals known for its ability to interact with nucleic acids was 1-chloro-2-[(2-chloroethyl)sulfanyl]ethane, also known as mustard gas [24]. This compound, as well as other alkylating agents, was shown to efficiently inactivate viruses, such as the tobacco mosaïc virus [25].…”

Section: Birth Of Rna Structure Probingmentioning

confidence: 99%

Chemical and Enzymatic Probing of Viral RNAs: From Infancy to Maturity and Beyond

Gilmer

Quignon

Jousset

et al. 2021

Viruses

View full text Add to dashboard Cite

RNA molecules are key players in a variety of biological events, and this is particularly true for viral RNAs. To better understand the replication of those pathogens and try to block them, special attention has been paid to the structure of their RNAs. Methods to probe RNA structures have been developed since the 1960s; even if they have evolved over the years, they are still in use today and provide useful information on the folding of RNA molecules, including viral RNAs. The aim of this review is to offer a historical perspective on the structural probing methods used to decipher RNA structures before the development of the selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE) methodology and to show how they have influenced the current probing techniques. Actually, these technological breakthroughs, which involved advanced detection methods, were made possible thanks to the development of next-generation sequencing (NGS) but also to the previous works accumulated in the field of structural RNA biology. Finally, we will also discuss how high-throughput SHAPE (hSHAPE) paved the way for the development of sophisticated RNA structural techniques.

show abstract

Section: Birth Of Rna Structure Probingmentioning

confidence: 99%

Chemical and Enzymatic Probing of Viral RNAs: From Infancy to Maturity and Beyond

Gilmer

Quignon

Jousset

et al. 2021

Viruses

View full text Add to dashboard Cite

show abstract

“…They found reactions with adenine and guanine, which they suggested formed thiazans at the exocyclic amino groups. Elmore, Gulland and Jordan (37) at Nottingham had also invoked amino groups in DNA as sites of attack by mustard gas from the application of their electrometric titration methods to alkylated DNA; they also suggested that the phosphodiester groups could be reactive.…”

Section: T~k 3~) mentioning

confidence: 99%

Alkylation of DNA and its aftermath

Lawley

1995

BioEssays

View full text Add to dashboard Cite

Current pharmacopoeias invariably refer to a category of 'alkylating drugs', still among the most widely used in cancer chemotherapy. They are described as acting through their ability to damage DNA, thus interfering with cell replication. Unfortunately, this mode of action implicates these drugs as carcinogens. Thus the early studies recalled in this essay proved to be relevant to our understanding of both the main problems with which cancer research concerns itself: the causation of cancer and possible methods of treatment of this group of diseases.

show abstract

“…Chemical modifications of nucleotides are a major cause of DNA damage and mutation; publications documenting the reaction of chemical mutagens with DNA date back to the late 1940s when Elmore et al (1) showed that mustard gas, bis (2-chloroethyl)sulfide, reacts with DNA in vitro . Later work demonstrated that mustard gas induces N 7-guanine alkylations in mouse DNA in vivo (2).…”

Section: Introductionmentioning

confidence: 99%

Quantitative relationships betweenlacZmutant frequency and DNA adduct frequency in Muta™Mouse tissues and cultured cells exposed to 3-nitrobenzanthrone

White

Douglas

Phillips

et al. 2017

MUTAGE

View full text Add to dashboard Cite

The frequency of stable DNA adducts in a target tissue can be used to assess biologically effective dose; however, the utility of the metric in a risk assessment context depends on the likelihood that the DNA damage will be manifested as mutation. Previously, we employed the Muta™Mouse system to examine the induction of lacZ mutants and DNA adducts following exposure to the well-studied mutagenic carcinogen 3-nitrobenzanthrone (3-NBA). In this follow-up work, we examined the empirical relationships between total adduct frequency and mutant frequency (MF) in tissues and cultured cells following acute 3-NBA exposure. The results show a significant induction of DNA damage and lacZ mutants in liver, colon and bone marrow, as well as FE1 pulmonary epithelial cells. In contrast, lung and small intestine samples had low, but significantly elevated adduct levels, with no significant increases in lacZ MF. Additional analyses showed a significant relationship between the mutagenic efficiency of total adducts, measured as the slope of the relationships between MF and total adduct frequency, and tissue-specific mitotic index (MI). The lack of mutation response in lung, in contrast to the high in vitro MF in FE-1 lung cells, is likely related to the 100-fold difference in MI. The lack of small intestine mutagenic response may be related to limited metabolic capacity, differences in DNA repair, and /or chemically induced apoptosis that has been observed for other potent mutagens. The results indicate that interpretation of adduct frequency values in a risk assessment context can be improved by considering the MI of the target tissue; however, more generalised interpretation is hampered by tissue-specific variations in metabolic capacity and damage processing. The work provides a proof of principle regarding the use of the Muta™Mouse system to critically examine the health risks associated with tissue-specific adduct loads.

show abstract

The reaction of nucleic acids with mustard gas

Cited by 59 publications

References 11 publications

Chemical and Enzymatic Probing of Viral RNAs: From Infancy to Maturity and Beyond

Chemical and Enzymatic Probing of Viral RNAs: From Infancy to Maturity and Beyond

Alkylation of DNA and its aftermath

Quantitative relationships betweenlacZmutant frequency and DNA adduct frequency in Muta™Mouse tissues and cultured cells exposed to 3-nitrobenzanthrone

Contact Info

Product

Resources

About