Hydroquinone: genotoxicity and prevention of genotoxicity following ingestion.
Plant-derived polyphenolics and other chemicals with antioxidant properties have been reported to inhibit the expression of genotoxic activity by pro-oxidant chemicals (Sai et al., 1992, 1994; Teel and Castonguay, 1992). In vitro and in vivo studies with ionizing radiation suggest that hydroquinone (HQ) may have similar protective effects (Babaev et al., 1994). The present study was conducted to determine whether HQ is capable of inhibiting the induction of micronuclei in the bone marrow of mice following exposure to an oxidant, potassium bromate or KBrO3 (Nakajima et al., 1989; Sai et al., 1992, 1994). To be able to interpret the results of this work, it was also necessary to determine whether HQ is itself genotoxic when fed in the diet. HQ diets (0.8%) fed to mice for 6 days reduced the background incidence of micronuclei compared with the basal diet. KBrO3 dosed ip (12.5-100 mg/kg) produced a dose-dependent increase in micronuclei as reported by others. Mice fed 0.8% HQ diets 6 days, and then dosed intraperitoneally with KBrO3, showed a 36% reduction in micronuclei across the range of KBrO3 dose levels. This effect was associated with a reduction in the background micronucleus response as well as a reduction in response to KBrO3. Statistical significance (P < or = 0.05), observed at a dose of 25 mg/kg KBrO3 in the mice fed the control diet, was abolished in the group fed 0.8% HQ. When mice were given 50 mg HQ/kg by oral gavage and then given 50 mg KBrO3/kg ip 20 min later, the micronucleus response induced by KBrO3, was lower in animals given HQ. The results of this study demonstrate that large doses of HQ may be given orally without induction of micronuclei or bone marrow depression, that HQ reduces the background micronucleus response in animals fed a basal diet, and that the HQ reduces the micronucleus response to KBrO3 as well as background incidence of micronuclei in KBrO3-dosed animals. The protective effect of HQ may be due to enzyme induction or a direct antioxidant effect of HQ against oxidants commonly present in the diet.
O'Donoghue
J
J
Health and Environment Laboratories, Eastman Kodak Company, Rochester, NY 14652-6256, USA.
Barber
E D
ED
Hill
T
T
Aebi
J
J
Fiorica
L
L
D000284:Administration, Oral; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000648:ultrastructure; D001959:Bromates / Q000008:administration & dosage / Q000633:toxicity*; D004032:Diet; D004347:Drug Interactions; D005260:Female; D006873:Hydroquinones / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*
D016587:Antimutagenic Agents; D001959:Bromates; D006873:Hydroquinones; D009153:Mutagens; C019536:potassium bromate; C031927:hydroquinone