Cytotoxicity of some potential DNA intercalators (carbazole, acridine and anthracene derivatives) evaluated through neutrophil chemiluminescence.
A modifying effect of potential DNA intercalators, belonging to a group of carbazole, acridine and anthracene derivatives, on the course of luminol-dependent chemiluminescence of neutrophils (polymorphonuclear leucocytes; PMNL) in the process of phagocytosis was studied. This effect was also examined in reactive-oxygen-species-generating non-cellular reaction systems consisted of myeloperoxidase or xanthine oxidase. Adriamycin (Doxorubicin), which is widely applied to neoplasm therapy, was used as a reference intercalator in the conducted experiments. It was demonstrated that some structurally different derivatives of carbazole inhibited the light emission from N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced neutrophils to the same degree as adriamycin. It can be suggested that the same inhibitory effect was caused by either a different cellular distribution of the derivatives or different interactions of the derivatives with reactive oxygen species in the investigated systems. Measurements of chemiluminescence suggested that the thiol group in one of the carbazole derivatives could strongly interfere with oxidative cell metabolism. In contrast to the analogous derivative of carbazole, both anthracene and acridine derivatives, possessing an N-1'-hydroxyethyl-ethylenodiamino group, induced different increases in chemiluminescence accompanying the process of neutrophil phagocytosis. Cytotoxicity of the investigated derivatives, being tested previously in cancer cells with a sulphorhodamine B assay, was found to possess a specific representation in the complex picture of the derivative-caused modification both of neutrophil and enzymatic non-cellular chemiluminescence. We suggest that chemiluminescence assays may serve as a helpful tool in the primary screening of drug cytotoxicity.
Sajewicz
W
W
Department of Toxicology, Wroclaw University of Medicine, Traugutta 57/59, PL-50417 Wroclaw, Poland. amtox@polbox.com
Dlugosz
A
A
D000079:Acetaldehyde / Q000378:metabolism; D000166:Acridines / Q000633:toxicity; D000328:Adult; D000873:Anthracenes / Q000633:toxicity; D002227:Carbazoles; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007364:Intercalating Agents / Q000633:toxicity*; D008163:Luminescent Measurements; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D014969:Xanthine Oxidase / Q000378:metabolism
D000166:Acridines; D000873:Anthracenes; D002227:Carbazoles; D007364:Intercalating Agents; C041514:carbazole; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009195:Peroxidase; D014969:Xanthine Oxidase; D000079:Acetaldehyde