Ethylnitrosourea

Ethylnitrosourea, commonly abbreviated ENU and also known as N-ethyl-N-nitrosourea, is a small, highly reactive nitrosourea alkylating agent used primarily as a chemical mutagen in genetic research. It is employed to induce random point mutations in a variety of organisms, including plants, invertebrates, and mammals, making it a standard tool for forward-genetic screens in model systems such as mice.

ENU acts as a potent alkylating agent that decomposes to reactive intermediates capable of transferring an ethyl group to DNA. The major DNA adducts are O6-ethylguanine and N7-ethylguanine, with additional lesions at N3-ethyladenine. These ethylated bases can mispair during DNA replication, producing heritable point mutations. ENU is among the most efficient chemical mutagens used for generating mutations in germ cells.

In practice, ENU is used to generate mutant mouse libraries for phenotype–genotype correlation studies and to explore gene function through loss-of-function or altered-function mutations. Its high mutagenic potency means that relatively small doses can yield detectable and heritable changes, though the resulting mutation spectrum is broad and can include lethal events.

Safety and handling: ENU is highly toxic and carcinogenic; handling is restricted to specialized facilities with appropriate engineering controls and personal protective equipment. Exposure must be minimized, and disposal must comply with stringent regulatory requirements. ENU is not used as a therapeutic agent in humans due to its mutagenic properties.

History and notes: ENU has been a cornerstone of mutagenesis research since the mid-20th century and remains a key tool in modern genetics, particularly for generating novel model organisms and studying gene function.