Calyculin A, a non-phorbol ester type tumor promotor, induced oxidative DNA damage in stimulated human neutrophil-like cells.
Calyculin A(CA) induced 8-hydroxydeoxyguanosine (8OHdG), typical of mutagenic oxidative DNA damage, in N-Formyl-Methionyl-Leucyl-Phenylalanine (FMLP)-stimulated dimethyl sulfoxide(DMSO)-differentiated HL60(DMSO-HL60), which has characteristics similar to those of human neutrophils. CA enhanced O2-generation in FMLP-stimulated DMSO-HL60. CA by itself neither induced 8OHdG nor O2-generation. FMLP by itself induced O2-generation, however, it did not induce 8OHdG. These findings suggest that CA exerts its tumor promotion activity through modulating O2-generation and through inducing oxidative DNA damage and that a common bioactive peptide induces oxidative DNA damage under a certain condition.
Takeuchi
T
T
Department of Hygiene and Preventive Medicine, Osaka University School of Medicine, Japan.
Nakajima
M
M
Morimoto
K
K
D000080242:8-Hydroxy-2'-Deoxyguanosine; D002273:Carcinogens / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008387:Marine Toxins; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010080:Oxazoles / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D002273:Carcinogens; D008387:Marine Toxins; D010080:Oxazoles; D017382:Reactive Oxygen Species; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; C059041:calyculin A; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002374:Catalase; D005979:Glutathione Peroxidase; D003849:Deoxyguanosine; D004121:Dimethyl Sulfoxide