The pentachlorophenol metabolite tetrachloro-p-hydroquinone induces the formation of 8-hydroxy-2-deoxyguanosine in liver DNA of male B6C3F1 mice.
Tetrachloro-p-hydroquinone (TCHQ), the major metabolite of pentachlorophenol (PCP) in mammalian systems, is known to autoxidize to its semiquinone radical under physiological conditions. In this way, PCP could present a potent source of reactive oxygen species (ROS) during metabolization. ROS contribute to numerous modifications of DNA. Formation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG), a product of hydroxyl radical attack on DNA, is monitored as a marker of a major genetic lesion induced by agents which produce oxygen radicals. We studied the properties of TCHQ for the induction of oxidative DNA damage in vivo. Male B6C3F1 mice were fed a diet containing TCHQ for 2 and 4 weeks. These experiments resulted in an enhancement of about 50% of the 8-OH-dG portion in liver DNA after administration of 300 mg TCHQ/kg body wt./day for 2 weeks. Control levels did not change over the periods of 2 and 4 weeks, respectively. In contrast to these results, a single i.p. injection of 20 or 50 mg/kg body wt. did not affect the 8-OH-dG content after 6 and 24 h, respectively. These data may support a possible contribution of ROS to the carcinogenicity of PCP.
Dahlhaus
M
M
Abteilung für Pflanzenbehandlungs-, Schädlingsbekämpfungs- und Holzschutzmittel, Max von Pettenkofer-Institut, Berlin, Germany.
Almstadt
E
E
Appel
K E
KE
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D004247:DNA / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D004032:Diet; D006873:Hydroquinones / Q000008:administration & dosage / Q000633:toxicity*; D017665:Hydroxyl Radical; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction; D010416:Pentachlorophenol / Q000378:metabolism; D017382:Reactive Oxygen Species
D006873:Hydroquinones; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; C044578:2,3,5,6-tetrachlorohydroquinone; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D010416:Pentachlorophenol; D003849:Deoxyguanosine