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oai:mountainscholar.org:10217/2376282025-12-30T03:42:07Zcom_10217_100532com_10217_100000com_10217_100362com_10217_100303col_10217_100538col_10217_100364

Carsten, Ronald E., author Ullrich, Robert L., advisor 2024-03-13T18:50:56Z 2024-03-13T18:50:56Z 2008 ETDF_Carsten_2008_3346423.pdf https://hdl.handle.net/10217/237628 https://doi.org/10.25675/3.018999 Resveratrol has been shown to have cancer preventive properties. It modulates a wide range of molecular targets including those involved with induction of apoptosis and cell cycle arrest in a concentration dependent fashion. This study was designed to investigate resveratrol's ability to reduce radiation-induced chromosome aberrations and PU.1 gene loss in mouse bone marrow cells. Loss of 1 PU.1 gene and missense mutation of the remaining allele leads to acute myeloid leukemia in CBA mice. Male CBA mice were divided into groups of 10 mice. Control groups consisted of no treatment, resveratrol, muscadine grape extract (MGE), and radiation with end points of 1, 7, and 30 days post-irradiation. Experimental groups were administered resveratrol starting 2 days before irradiation with bone marrow collected at 1 and 30 days; resveratrol initiated 2 hours (as a single dose or continued to the end point) or started 2 days (continued to the end point) after irradiation with collection at 1, 7, and 30 days; and resveratrol or MGE at specified doses starting 2 days before irradiation with bone marrow collection1 day after radiation exposure. Cytogenic evaluation and fluorescence in situ hybridization was performed. Resveratrol significantly (p<0.05) reduced mean chromosome aberrations at all end points when initiated before or after irradiation. The optimal dose for reducing chromosome aberrations at day 1 for resveratrol alone was 6.25-25 mg/kg and for resveratrol in MGE was 2.10-7.13 μg/kg. Loss of the PU.1 gene was significantly (p<0.0001) reduced at 1 or 30 days with resveratrol and MGE administration. When initiated pre-irradiation, resveratrol reduced chromosome aberrations and PU.1 loss at 1 and 30 days, indicating radioprotection. Cancer prevention was implied when resveratrol was initiated after irradiation resulting in reduced chromosome aberrations at 1, 7, and 30 days and reduced PU.1 gene loss at 1 and 30 days. Resveratrol pre-irradiation was not more beneficial than a single dose 2 hours post-irradiation (p>0.05) at 30 days; resveratrol initiated pre-irradiation was more effective (p<0.05) than continued resveratrol started 2 days post-irradiation at 30 days. The μg/kg dose of resveratrol found in MGE was significantly more effective than the mg/kg dose of resveratrol. born digital doctoral dissertations English eng Colorado State University. Libraries 2000-2019 Copyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright. Per the terms of a contractual agreement, all use of this item is limited to the non-commercial use of Colorado State University and its authorized users. acute myeloid leukemia resveratrol molecular biology cellular biology medicine oncology In-vivo investigation of resveratrol as a preventive for radiation-induced acute myeloid leukemia Text Doctor of Philosophy (Ph.D.) Doctoral Cell and Molecular Biology Colorado State University This Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). open.access