Sarin biomarkers

IMPA, the major metabolite of diisopropyl methylphosphonate, has been suggested as a possible biomarker of exposure for diisopropyl methylphosphonate. The excretion of IMPA is not unique to diisopropyl methylphosphonate exposure IMPA is also a major metabolite of GB (Sarin) (Little et al. 

Exposure. No biomarkers of exposure were identified that were specific to diisopropyl methylphosphonate. Although standard procedures exist for identifying diisopropyl methylphosphonate s primary metabolite (IMP A) in plasma, urine, and feces (Weiss et al. 1994), the detection of IMP A is not unique to diisopropyl methylphosphonate exposure. IMPA is also a major metabolite of GB (Sarin) (Little et al. 1986). In addition, IMPA is cleared from the body rapidly, making it a useful indicator for recent exposure only. 

Abu-Qare, A.W., Abou-Donia, M.B. (2001). Combined exposure to sarin and pyridostigmine bromide increased levels of rat urinary 3-nitrotyrosinee and 8-hydroxy-2 -deoxyguanosine, biomarkers of oxidative stress. Toxicol. Lett. 123 51-8. 

These examples show that OPs can bind covalently to albumin under physiological conditions, and that the resultant adducts are relatively stable. OP-albumin adducts could therefore be useful as biomarkers of OP exposure. In addition, unlike cholinesterases, the soman-albumin conjugate does not age (Li et al, 2008a), making it possible to discriminate between sarin and soman exposure. OP-albumin adducts have not yet been reported in humans exposed to OPs. 

Black et al. (1999) found that sarin and soman bind to a tyrosine residue in human plasma and suggested that this could form the basis of a biomarker of exposure to these agents. 

Because of its high concentration in human plasma, BChE is also used as a biomarker for detection of exposure to OP pesticides and nerve agents. Hence, the sensor was likewise evaluated for detection of BChE-OP biomarkers. The detection method is the same as the protocol described previously in section 4.1 however, the chemical nerve agent (stracturally similar to Sarin) diisopropyl fluorophosphate (DFP) was chosen as a model OP in this studies. 

Tyrosine adducts were found in guinea pigs and marmosets poisoned with sarin, soman, cyclosarin, and tabun. VX, which is less reactive than other WNAs, formed an adduct in human plasma in vitro only at high concentrations (Williams et al., 2007 Black, 2010 Black and Read, 2013). Tyrosine adducts were less sensitive than ChE as biomarkers with respect to exposure levels but were more stable and did not undergo an aging reaction such as OP binding to serine esterases (Read et al.,... 

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