Mutagenicity and dark toxicity of the second-generation photosensitizer bacteriochlorin a

Bacteriochlorin a (BCA) is an effective second-generation photosensitizer b oth in vitro and in vivo. BCA has a high molecular absorption coefficient ( 32 000 M-1 cm(-1)) at 760 nm. At this wavelength tissue penetration of ligh t is almost optimal and melanin absorption is relatively low. BCA is prefer entially retained in a number of tumour model systems and is rapidly cleare d from non-cancerous tissues, thus inducing no or minor skin photosensitivi ty. Mutagenicity of BCA has been tested using the Salmonella typhimurium st rains TA97, TA98, TA100, TA102 and TA104. In all tester strains used, BCA i nduces, in the dark, a minute increase in the number of revertants. No line ar correlation between the number of revertants and the BCA dose is observe d. Incubation of isolated rat hepatocytes with BCA, in the dark, does not r esult in increased cell death as measured by leakage of cytosolic lactate d ehydrogenase. A convenient bioassay to test possible genotoxicity in vivo i s the established Somatic Mutation and Recombination Test (SMART) on Drosop hila melanogaster. Bacteriochlorin was tested for induction of loss of hete rozygosity in the white/white(+) eye mosaic assay, which predominantly meas ures homologous mitotic recombination in somatic cells of Drosophila after treatment of larval stages. BCA did not induce loss of heterozygosity above the level of the incorporated controls, with or without illumination. Base d on these results, obtained in prokaryotic and eukaryotic cells and in viv o, we are inclined to conclude that the dark toxicity and mutagenic propert ies of BCA, as measured by the applied bioassays, are negligible. (C) 1998 Elsevier Science S.A. All rights reserved.