title: Zinc deficiency enhances the induction of micronuclei and 8-hydroxy-2'-deoxyguanosine via superoxide radical in bone marrow of zinc-deficient rats.
abstract: The aim of the present study was to examine whether zinc (Zn) deficiency augmented the frequency of micronuclei, an indicator of chromosome aberration, and the induction of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of cellular DNA damage derived from oxidative stress, in rat bone marrow cells or not. Both the frequency of micronuclei and the induction of 8-OHdG were significantly increased in rats fed with a Zn-deficient versus a standard diet for 6 weeks (p < 0.005). The supplementation of Zn with a standard diet for 4 weeks to rats fed with a Zn-deficient diet for 6 weeks restored the enhanced induction of micronuclei and 8-OHdG to levels comparable to those seen in rats fed with a standard diet for 10 weeks, indicating that the shortage of Zn in the body is involved in the induction of micronuclei and 8-OHdG. Again, the membrane-permeable superoxide dismutase mimetic superoxide scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl, treatment (100 μmol/kg, twice a day) for 10 days prior to the termination of dietary treatment reduced the induction of micronuclei and 8-OHdG in rats fed with a Zn-deficient diet for 6 weeks to levels comparable to those in rats fed with a standard diet for 6 weeks, indicating that superoxide radical participates in the induction of micronuclei and 8-OHdG. In fact, the endogenous superoxide scavenger, Cu/Zn superoxide dismutase, was significantly reduced in the bone marrow cells of rats fed with a Zn-deficient diet for 6 weeks when compared to those of rats fed with a standard diet for 6 weeks (p < 0.005). These observations demonstrate that Zn deficiency elevates the frequency of micronuclei and the induction of 8-OHdG through an increase in the biological action of the superoxide radical. This suggests an increase in carcinogenic initiation resulting from Zn deficiency-induced oxidative stress.
authors.affiliation: Department of Public Health and Environmental Medicine, Faculty of Medicine, The Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo 105-8461, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawasaki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yanagisawa
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight; D001853:Bone Marrow / Q000473:pathology*; D003300:Copper / Q000097:blood; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D004032:Diet; D019587:Dietary Supplements; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000737:chemistry*; D015032:Zinc / Q000097:blood / Q000172:deficiency* / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D013481:Superoxides; D003300:Copper; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D015032:Zinc