Mustard gas, used in chemical warfare since 1917, is a mutagenic and
carcinogenic agent that produces severe dermal lesions for which there are no
effective therapeutics; it is currently seen as a potential terrorist threat to
civilian populations. Sulforaphane, found in cruciferous vegetables, is known to
induce enzymes that detoxify compounds such as the sulfur mustards that react
through electrophilic intermediates. Here, we observe that a single topical
treatment with sulforaphane induces mouse epidermal levels of the regulatory
subunit of glutamate-cysteine ligase, the rate-limiting enzyme in glutathione
biosynthesis, and also increases epidermal levels of reduced glutathione.
Furthermore, a glutathione S-transferase, GSTA4, is also induced in mouse skin
by sulforaphane. In an in vivo model in which mice are given a
single mutagenic application of the sulfur mustard analog 2-(chloroethyl) ethyl
sulfide (CEES), we now show that therapeutic treatment with sulforaphane
abolishes the CEES-induced increase in mutation frequency in the skin, measured
four days after exposure. Sulforaphane, a natural product currently in clinical
trials, shows promise as an effective therapeutic against mustard gas.