Physiological testing for Hexavalent Chrome exposure in the human body

ABSTRACT: Caldera Pharmaceuticals proposes to develop physiologic biomarkers requested by the US Air Force to quantify workplace exposure to hexavalent chrome (Cr+6). Exposure to Cr+6 is dangerous and unwanted, because it is a primary carcinogen (class 1 International Agency for Research on Cancer / IARC) and a known lung cancer carcinogen. Chromium (Cr) exists in several valence states, the most prevalent states are hexavalent Cr (Cr+6, which is associated with industrial exposure and toxicity) and trivalent Cr (Cr+3, which is stable and a biologically active form). Cr+3 is an essential nutrient for humans and shortages may cause heart conditions and metabolic disruptions or diabetes; it is classified as IARC Group 3. Although a limited amount of Cr+3 is necessary, large amounts may be hazardous. Cr supplements are taken readily and are available as trivalent Cr in chloride (CrCl3) or picolinate (CrPic) salt forms, but associated health effects are unknown. If ingested in large amounts, both Cr+3 and +6 can cause gastrointestinal problems and ulcers, or kidney and liver damage. There are no physiologic biomarkers for exposure to Cr+6, especially those that differentiate between various Cr species in vivo. Caldera XRpro(R) Technology will be used to screen for Cr-selective biomarker aptamers. BENEFIT: Military personnel are an important cohort that is exposed to Cr+6; accurate and inexpensive biomarker assays developed in the project may also be used for mitigation of exposure effects to personnel, and environmental monitoring/abatement. These increase the commercial appeal of the products. XRpro offers reagent availability and low cost that are key to the success of the products. Biomarker agents developed in Phase I have multiple usages including environmental monitoring and abatement, markers of exposure in vivo, therapeutic chelation of only dangerous metals, without harm to useful elements such as zinc and selenium. Drug and biomarker discovery/development costs are extremely expensive. The proposed project solves this problem by using low cost and better data acquisition methods provided by Caldera XRpro screening. Library screening is less expensive and provides better, full elemental data, resulting in more available, stable, and effective formulation, selectivity, sensitivity, and specificity. Many cellular factors are regulated through variable phosphorylation, metallation, and glycosylation. XRpro simultaneously assesses metal cofactors, collecting quantitative data on 24 elements such as sulfur (S, from peptides), calcium (Ca), zinc (Zn), selenium (Se), copper (Cu), iron (Fe), phosphorus (P), etc. No other available technology screens for metal selectivity so rapidly.