Formation of 8-hydroxyguanine in DNA during mitomycin C activation.
DNA damage caused indirectly via reactive oxygen species generated during reductive activation of mitomycin C was evaluated. This oxidative DNA damage was measured by determining the formation of 8-hydroxyguanine in DNA exposed to chemically or enzymatically activated mitomycin C. The level of 8-hydroxyguanine was measured indirectly by determining formamidopyrimidine-DNA glycosylase-sensitive sites induced in plasmid DNA exposed to mitomycin C and directly by a 32P-postlabeling assay for the modified base. Activation of mitomycin C by sodium borohydride in air, by H2/Pt, or xanthine oxidase in N2 caused increases in the level of 8-hydroxyguanine. The extent of the increase varied according to the incubation conditions with the greatest increase being observed in DNA exposed to mitomycin C activated under hypoxic conditions. These results support a possible indirect mechanism for DNA damage caused by mitomycin C that is mediated by reactive oxygen species.
Maccubbin
A E
AE
Grace Cancer Drug Center, Buffalo, NY, USA.
Ersing
N
N
Budzinski
E E
EE
Box
H C
HC
Gurtoo
H L
HL
D000693:Anaerobiosis; D001894:Borohydrides; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004249:DNA Damage; D043382:DNA-Formamidopyrimidine Glycosylase; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis; D016685:Mitomycin / Q000494:pharmacology*; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D010957:Plasmids / Q000737:chemistry / Q000187:drug effects; D013379:Substrate Specificity; D014969:Xanthine Oxidase
D001894:Borohydrides; D010761:Phosphorus Radioisotopes; D016685:Mitomycin; C024829:8-hydroxyguanine; D006147:Guanine; C025364:sodium borohydride; D004247:DNA; D014969:Xanthine Oxidase; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase