Radical-mediated modification of deoxyguanine and deoxyribose by luteoskyrin and related anthraquinones.
When cultured Reuber hepatoma H4-II-E and fibroblast Balb/3T3 cells were exposed to various concentrations of 5 derivatives of anthraquinones, luteoskyrin, a bis-anthraquinoid hepatocarcinogenic mycotoxin, exhibited the highest cytotoxicity to these cell lines. The content of 8-hydroxydeoxyguanine residues in the DNA of H4-II-E cells was dose- and time-dependently increased by luteoskyrin. The tumorigenic anthraquinones such as rugulosin and danthron also slightly elevated the level of this modified DNA base, while no such modification was observed with chrysophanol and emodin. Detailed experiments with luteoskyrin have demonstrated the formation of 8-hydroxydeoxyguanine and the degradation of deoxyribose into thiobarbituric acid-reactive products in the presence of ascorbic acid. These findings suggest the possible involvement of anthraquinone-derived hydroxy radicals for the modification of DNA base and deoxyribose.
Akuzawa
S
S
Department of Toxicology and Microbial Chemistry, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
Yamaguchi
H
H
Masuda
T
T
Ueno
Y
Y
D016475:3T3 Cells; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D003855:Deoxyribose / Q000378:metabolism*; D006878:Hydroxides; D017665:Hydroxyl Radical; D051379:Mice; D009285:Naphthoquinones / Q000494:pharmacology*
D000880:Anthraquinones; D006878:Hydroxides; D009285:Naphthoquinones; C100224:luteoskyrin; D017665:Hydroxyl Radical; D003855:Deoxyribose; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine