Penetration and haptenation of p-phenylenediamine.

Although p-phenylenediamine (PPD) has been recognized as an extreme sensitizer for many years, the exact mechanism of sensitization has not been elucidated yet. Penetration and the ability to bind to proteins are the first two hurdles that an allergen has to overcome to be able to sensitize. This review is an overview of studies regarding PPD penetration through skin (analogues) and studies on the amino acids that are targeted by PPD.

Cyanamide-mediated Inhibition of N-acetyltransferase 1.

Cyanamide has been used for decades for medical intentions in the treatment of alcoholism and for agricultural purposes as a plant growth regulator and bud-breaking agent. Its therapeutic effect is mediated by reversible inhibition of aldehyde dehydrogenase and it was reported to be metabolized in vivo mainly via coenzyme A dependent N-acetylation by N-acetyltransferases. Although described to be a substrate for N-acetyltransferases (NATs), cyanamide has a different molecular structure to arylamines and hydrazines, the preferred substrates for N-acetyltransferases.

Variable NAT1 enzyme activity in long-term cultured human HaCaT keratinocytes.

Since animal testing should be avoided whenever possible, the development of in vitro tests for predicting the effect of chemicals becomes a major field. This rise of in vitro test systems led to an increased requirement for well-characterized continuously growing cell lines. Monitoring of the cells during test and routine culture is necessary to gain relevant and reproducible results.

Characterization of N-acetyltransferase 1 activity in human keratinocytes and modulation by para-phenylenediamine.

N-acetyltransferase 1 (NAT1)-mediated N-acetylation in keratinocytes is an important detoxification pathway for the hair dye ingredient para-phenylenediamine (PPD). Because NAT1 can be regulated by various exogenous compounds, including some NAT1 substrates themselves, we investigated NAT1 expression in keratinocytes and the interactions between PPD and NAT1. NAT1 activity was found to be cell-cycle phase-dependent.