Application of the direct peptide reactivity assay (DPRA) to inorganic compounds: a case study of platinum species

Toxicology Research
Jocelyn D C HemmingMartin M Shafer

Abstract

The in chemico Direct Peptide Reactivity Assay (DPRA) was developed as a non-animal, relatively high throughput, screening tool for skin sensitization potential. Although the Adverse Outcome Pathway (AOP) for respiratory sensitization remains to be fully elucidated, it is recognized that the molecular initiation event for both skin and respiratory sensitization to low molecular weight chemicals involves haptenation with proteins. The DPRA examines the reactivity of a test compound to two model peptides (containing either cysteine or lysine) and consequently is able to screen for both skin and respiratory sensitization potential. The DPRA was primarily developed for and validated with organic compounds and assessment of the applicability of the assay to metal compounds has received only limited attention. This paper reports the successful application of the DPRA to a series of platinum compounds, including hexachloroplatinate and tetrachloroplatinate salts, which are some of the most potent chemical respiratory sensitizers known. Eleven platinum compounds were evaluated using the DPRA protocol as detailed by Lalko et al., with only minor modification. Two palladium compounds with structures similar to that of the platinum specie...Continue Reading

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Citations

May 19, 2021·Toxicological Sciences : an Official Journal of the Society of Toxicology·Nora L KrutzG Frank Gerberick

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Methods Mentioned

BETA
Assay
peptide assay
cysteine

Software Mentioned

SCIEX Analyst
SigmaPlot

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