Lewisite biotransformation

FIGURE 56.8 Lewisite biotransformation, adduct formation, and its reversal. 

Vesicants, including sulfur mustard and lewisite, are the subject of the second main part of this chapter. Coherences of invasion and distribution are presented, and the major processes of biotransformation and elimination caused by binding to proteins [and more prominently, to deoxyribonucleic acid (DNA)] are discussed. Finally, we make some comments about current bioanalytical approaches. This chapter provides readers with a comprehensive overview of tire toxicokinetics of OP nerve agents and vesicants. 

Once incorporated, unbound lewisite is quickly hydrolyzed. Its predominant biotransformation product is 2-chlorovinylarsonous acid (CVAA Figure 56.8). Analytical methods to confirm lewisite exposure have focused on detection and quantification of CVAA, at least in the past. However, Noort et al. (2002) also pointed out that, due to the high affinity of arsenic toward sulfhydryl groups, adducts of lewisite/CVAA and cysteine residues of proteins are formed. In an in vitro study, incubating 14C-labeled lewisite with human blood samples, 90% of lewisite was found in erythrocytes, whereas 25-50% of arsenic was boxmd to globin. 

From these protein adducts, CVAA can be released to form an adduct with the antidote British anti-lewisite (BAL Fidder et al., 2000). The authors were also able to identify a specific protein adduct of lewisite formed with cysteine residues 93 and 112 of p-globin. See the section "Detection of DNA and protein adducts of vesicants," later in tiiis chapter, for analytical details. Figure 56.8 summarizes the biotransformation and reversal of adduct formation by BAL. 

Methods to detect lewisite exposure have been focused on its main biotransformation product, CVAA. Initial methods were developed for environmental samples (Bossle et al., 1989). Methods for CVAA quantification in serum were described by Fowler et al. (1991), as well as Jakubowski et al. (1993). CVAA was derivatized with... 

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