Light irradiation increases embryotoxicity of photodynamic therapy sensitizers (5-aminolevulinic acid and protoporphyrin IX) in chick embryos.
Photodynamic therapy (PDT) of malignant processes is based on the ability of a photosensitizer to first, accumulate in malignant (immature) tissue and second, to be destroyed following light irradiation. Because of the similarity between malignant and embryonic immature tissues, we investigated the deleterious effect of the PDT procedure on day 4 chick embryos in ovo. We compared experimentally the photodynamic effect (light-toxic) and the side effect (dark-toxic) of the clinically attractive photosensitizers 5-aminolevulinic acid (ALA) and protoporphyrin IX (PP IX). The dark and light embryotoxicity (i.e. lethality plus teratogenicity) was determined after intra-amniotic injection of one of a range of dose of each compound. Under dark conditions, PP IX exhibited embryotoxicity at a dose of 10 microg/embryo; however ALA did not exhibit embryotoxicity even at the highest dose (300 microg/embryo). Light irradiation of embryos following injection induced strong embryotoxic effects of both substances even at dark-ineffective doses.
Peterka
M
M
Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic. Peterka@sun2.biomed.cas.cz
Klepácek
I
I
D000014:Abnormalities, Drug-Induced; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D002642:Chick Embryo / Q000187:drug effects* / Q000528:radiation effects*; D003624:Darkness / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D020964:Embryo Loss / Q000139:chemically induced*; D008027:Light / Q000009:adverse effects*; D008081:Liposomes; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000633:toxicity*; D011524:Protoporphyrins / Q000008:administration & dosage / Q000633:toxicity*
D008081:Liposomes; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX