SHORT-TERM BACTERIAL TESTS AS A CONVENIENT ME- THOD FOR SCREENING ASSESSMENT OF PHOTOGENOTOXIC PROPERTIES OF PHARMACEUTICALS

Sunlight is known to produce toxic effects in humans. Adverse biological effects of UV radiation can be enhanced by some chemical compounds which additionally absorb UV energy and are known as photosensitizers. A number of light-absorbing pharmaceuticals are known to cause photoirritation, phototoxic or photo-allergic effects, and several guidelines on photo-safety testing of drugs have been published. However, there is still a need to develop a battery of tests for fast and reliable assessment of photogenotoxicity of pharmaceuticals. In this study, photogenotoxicity of chlorpromazine, a UV-absorbing compound, was investigated using two shortterm bacterial tests: the SOS Chromotest and the umu-test. The aim was to develop a new protocol for these screening tests to enable rapid initial evaluation of genotoxic properties of pharmaceuticals after UV irradiation. Chlorpromazine was not genotoxic under standard short-term bacterial testing conditions, i.e. in tests carried out without exposure to light. As intermediates formed after UVA irradiation are short-lived ones, standard testing procedures were modified. The tested compound and the bacterial strains were irradiated concomitantly during the test procedures Genotoxicity of chlorpromazine was demonstrated after UVA irradiation, but not after UVB irradiation which indicates that UVB does not cause the formation of genotoxic intermediates. Genotoxic properties of chlorpromazine after UVA and UVB irradiations were evaluated in agreement with published data which can indicate the convenience of our rapid tests as a first screen for preliminary assessment of photogenotoxicity in vitro. Chlorpromazine could be a positive control in the SOS Chromotest and the umu-test carried out under UV-irradiation conditions while the standard compounds used in these tests as positive controls are photo-labile.