It was demonstrated that the phenol NPrCAP, as a prohapten, can be activated in melanoma cells by tyrosinase to the reactive quinone-hapten NPrCAQ which binds to melanosomal proteins through their cysteine residues to form possible neo-antigens, thus triggering the immunological response (Figure 8).
Phenolic substrates as prohaptens are oxidized by tyrosinase to produce ortho-quinones, which act as haptens that covalently bind to tyrosinase or other melanosomal proteins to generate possible neoantigens [44, 53, 54].
In chemico evaluation of prohapten skin sensitizers: Behavior of 2-methoxy-4-(13C)methylphenol in the peroxidase peptide reactivity assay (PPRA) as an alternative to animal testing.
To study the effect of HaCaT keratinocytes on the response of THP-1 cells to sensitizers, we exposed THP-1 cells for 24 h in the absence and presence of HaCaT cells to a set of 14 sensitizers (6 haptens, 1 pre- and 7 prohaptens).
Separately focusing on the impact of HaCaT keratinocytes on the modulation of EC[DELTA]10 and EC[DELTA]50 values for haptens or prohaptens revealed that the chemicals for which potency was decreased were mainly haptens, while the majority of the chemicals for which potency was increased are prohaptens (acetaminophen, 3-aminophenol, 2-methoxy-4-methylphenol, resorcinol, cinnamic alcohol) (Fig.
So far, results obtained using the available methods show limitations in the demonstration of concentration-dependency and have limited capacities to detect certain prohaptens and for potency prediction (Piroird et al., 2015; Natsch et al., 2015; Nukada et al., 2012; Teunis et al., 2014; Jaworska et al., 2015; Urbisch et al., 2016; Adler et al., 2011).
Looking in more detail at the correlation of coculture data with in vivo potency data, we found that lower chemical concentrations were sufficient to induce a positive response for at least 46% of the tested sensitizers, among them mainly prohaptens, in the coculture model.
A skinlike cytochrome P450 cocktail activates prohaptens to contact allergenic metabolites.
Discrimination of haptens from prohaptens using the metabolically deficient Cpr(low/low) mouse.