In-vivo investigation of resveratrol as a preventive for radiation-induced acute myeloid leukemia
Date
2008
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Abstract
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.
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.
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acute myeloid leukemia
resveratrol
molecular biology
cellular biology
medicine
oncology