title: Modulation of hexavalent chromium-induced genotoxic damage in peripheral blood of mice by epigallocatechin-3-gallate (EGCG) and its relationship to the apoptotic activity.
abstract: This study was conducted to investigate the relationship between modulation of genotoxic damage and apoptotic activity in Hsd:ICR male mice treated with (-)-epigallocatechin-3-gallate (EGCG) and hexavalent chromium [Cr(VI)]. Four groups of 5 mice each were treated with (i) control vehicle only, (ii) EGCG (10 mg/kg) by gavage, (iii) Cr(VI) (20 mg/kg of CrO3) intraperitoneally (ip), and (iv) EGCG in addition to CrO3 (EGCG-CrO3). Genotoxic damage was evaluated by examining presence of micronucleated polychromatic erythrocytes (MN-PCE) obtained from peripheral blood of the caudal vein at 0, 24, 48, and 72 h after treatment. Induction of apoptosis and cell viability were assessed by differential acridine orange/ethidium bromide (AO/EB) staining. EGCG treatment produced no significant changes in frequency of MN-PCE. However, CrO3 treatment significantly increased number of MN-PCE at 24 and 48 h post injection. Treatment with EGCG prior to CrO3 injection decreased number of MN-PCE compared to CrO3 alone. The MN-PCE reduction was greater than when EGCG was administered ip. The frequency of early apoptotic cells was elevated at 48 h following EGCG, CrO3, or EGCG-CrO3 exposure, with highest levels observed in the combined treatment group, while the frequencies of late apoptotic cells and necrotic cells were increased only in EGCG-CrO3 exposure. Our findings support the view that EGCG is protective against genotoxic damage induced by Cr(VI) and that apoptosis may contribute to elimination of DNA-damaged cells (MN-PCE) when EGCG was administered prior to CrO3. Further, it was found that the route of administration of EGCG plays an important role in protection against CrO3-induced genotoxic damage.
authors.affiliation: a Unidad de Investigación en Genética y Toxicología Ambiental (UNIGEN), Facultad de Estudios Superiores "Zaragoza," Universidad Nacional Autónoma de México (UNAM), México D.F ., México.
authors.forename: María Del Carmen
authors.initials: Mdel C
authors.lastname: García-Rodríguez
authors.affiliation: a Unidad de Investigación en Genética y Toxicología Ambiental (UNIGEN), Facultad de Estudios Superiores "Zaragoza," Universidad Nacional Autónoma de México (UNAM), México D.F ., México.
authors.forename: Ana Rosa
authors.initials: AR
authors.lastname: Montaño-Rodríguez
authors.affiliation: a Unidad de Investigación en Genética y Toxicología Ambiental (UNIGEN), Facultad de Estudios Superiores "Zaragoza," Universidad Nacional Autónoma de México (UNAM), México D.F ., México.
authors.forename: Mario Agustín
authors.initials: MA
authors.lastname: Altamirano-Lozano
mesh_terms: D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002857:Chromium / Q000633:toxicity*; D017608:Chromium Compounds / Q000633:toxicity; D004249:DNA Damage; D004785:Environmental Pollutants / Q000633:toxicity*; D004912:Erythrocytes / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D009336:Necrosis
chemical_list: D016587:Antimutagenic Agents; D017608:Chromium Compounds; D004785:Environmental Pollutants; D009153:Mutagens; D002857:Chromium; C074702:chromium hexavalent ion; D002392:Catechin; C045651:epigallocatechin gallate; C023600:chromic oxide