In Vitro and In Vivo Research on Phototoxic Xenobiotics: Structure-Reactivity Relationships

Abstract

Simultaneous exposure to (sun)light and a xenobiotic may provoke phototoxic effects. Effects often concern the skin. However, normal photobiological processes in man, such as light-induces vitamin D3 production or the conversion of bilirubin with visible light, as well as animal experiments with xenobiotics (Beijersbergen van Henegouwen et al. 1988), show that systemic effects may also occur. Xenobiotics involved are present in drugs, cosmetics, food products, chemicals used in agriculture, the household, etc. The variety in molecular structure of phototoxic compounds is immense, which implies that they can be found in virtually all classes of xenobiotics. An important objective of research is to identify that part of the molecular structure of a given xenobiotic that causes the unwanted effects. This would provide an opportunity to alter the structure in such a way that the phototoxicity would be diminished whereas the desired properties of the xenobiotic, e.g., a drug, would be conserved. This aim may be achieved by combinating data from three different research lines:

• 1. Photoreactivity in vitro of the phototoxic xenobiotic and structure analogues whether or not in the presence of essential bio(macro)molecules

• 2. Phototoxicity in microbiological test systems (bacteria, yeast, mammalian cell cultures)

• 3. Phototoxicity in experimental animals