Mutagenicity and dark toxicity of the second-generation photosensitizer bacteriochlorin a.
Bacteriochlorin a (BCA) is an effective second-generation photosensitizer both 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 light is almost optimal and melanin absorption is relatively low. BCA is preferentially retained in a number of tumour model systems and is rapidly cleared from non-cancerous tissues, thus inducing no or minor skin photosensitivity. Mutagenicity of BCA has been tested using the Salmonella typhimurium strains TA97, TA98, TA100, TA102 and TA104. In all tester strains used, BCA induces, in the dark, a minute increase in the number of revertants. No linear correlation between the number of revertants and the BCA dose is observed. Incubation of isolated rat hepatocytes with BCA, in the dark, does not result in increased cell death as measured by leakage of cytosolic lactate dehydrogenase. A convenient bioassay to test possible genotoxicity in vivo is the established Somatic Mutation and Recombination Test (SMART) on Drosophila melanogaster. Bacteriochlorin was tested for induction of loss of heterozygosity in the white/white+ eye mosaic assay, which predominantly measures 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. Based on these results, obtained in prokaryotic and eukaryotic cells and in vivo, we are inclined to conclude that the dark toxicity and mutagenic properties of BCA, as measured by the applied bioassays, are negligible.
Schuitmaker
J J
JJ
Department of Ophthalmology, Leiden University Medical Center, Netherlands. J.J.Schuitmaker@mcb.medfac.leidenuniv.nl
Vogel
E W
EW
Nagelkerke
J F
JF
Bos
R P
RP
D000818:Animals; D002478:Cells, Cultured; D003624:Darkness; D004331:Drosophila melanogaster; D008099:Liver / Q000166:cytology; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects*
D017319:Photosensitizing Agents; D011166:Porphyrins; C065423:bacteriochlorin a