Teniposide (VM-26) treatment enhances the radiation-induced micronuclei in the bone marrow of mouse

Jagetia, Ganesh Chandra; Aruna, R

doi:10.1016/s0027-5107(99)00003-2

Cited by 7 publications

(4 citation statements)

References 33 publications

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“…An identical effect has been observed earlier with DOX and the other topoisomerase II inhibitors VM-26 and etoposide. 12,64,65 AME pretreatment inhibited the decline in PCE/NCE ratio, and the greatest effect was observed for 350 mg/kg AME. A similar effect has been reported earlier, in which captopril has been reported to inhibit the DOX-induced PCE/NCE ratio in mouse bone marrow.…”

Section: Discussionmentioning

confidence: 89%

Modulation of Doxorubicin-Induced Genotoxicity byAegle marmelosin Mouse Bone Marrow: A Micronucleus Study

et al. 2007

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The effect of various concentrations of Aegle marmelos (AME) on the doxorubicin (DOX)-induced genotoxic effects in mice bone marrow was studied. Treatment of mice with different concentrations of DOX resulted in a dose-dependent elevation in the frequency of micronucleated polychromatic (MPCE) as well as normochromatic (MNCE) erythrocytes in mouse bone marrow. The frequencies of MPCE and MNCE increased with scoring time, and the greatest elevation for MPCE was observed at 48 hours post-DOX treatment, whereas a maximum increase in MNCE was observed at 72 hours post-DOX treatment. This increase in MPCE and MNCE was accompanied by a decline in the polychromatic erythrocytes-normochromatic erythrocytes (PCE/NCE) ratio, which showed a DOX-dose-dependent decline. Treatment of mice with 200, 250, 300, 350, and 400 mg/kg body weight of AME, orally once daily for 5 consecutive days before DOX treatment, significantly reduced the frequency of DOX-induced micronuclei accompanied by a significant elevation in the PCE/NCE ratio at all scoring times. The greatest protection against DOX-induced genotoxicity was observed at 350 mg/kg AME. The protection against DOX-induced genotoxicity by AME may be due to inhibition of free radicals and increased antioxidant status.

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Section: Discussionmentioning

confidence: 89%

Modulation of Doxorubicin-Induced Genotoxicity byAegle marmelosin Mouse Bone Marrow: A Micronucleus Study

et al. 2007

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“…Radioprotective agents have been reported to give protection up to a particular dose; at higher concentrations, the effect may diminish [Thomson, 1962;Nagata et al, 1972;Baliga, 2002a, 2002b;Jagetia and Reddy, 2002;. Other authors have reported similar dose-responses for other types of radioprotective agents in HPBLs and other cell lines in vitro [Catena et al, 1996;Adiga, 1997, 2000;Adiga and Jagetia, 1999;Belyakov et al, 1999;Jagetia and Aruna, 1999;Vrinda and Uma Devi, 2001]. This phenomenon was also noted for MGN in the present study; 100 mg/ml of MGN was a slightly less effective radioprotector than 50 mg/ml, although the difference was not significant.…”

Section: Discussionmentioning

confidence: 99%

Effect of mangiferin on radiation-induced micronucleus formation in cultured human peripheral blood lymphocytes

Jagetia

Venkatesha

2005

Environ. Mol. Mutagen.

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Irradiation causes a variety of lesions in important biomolecules of the cell through generation of free radicals leading to genomic instability. DNA strand breaks, acentric fragments, or defective kinetochores are manifested as micronuclei after the first cell division. Chemicals that can trap free radicals may reduce the deleterious effects of ionizing radiation. Mangiferin (MGN), a glucosylxanthone derived from Mangifera indica (mango), was investigated for its ability to reduce the frequency of radiation-induced micronucleated binucleate cells (MNBNCs) in cultured human peripheral blood lymphocytes (HPBLs). HPBL cultures were pretreated with 0, 5, 10, 20, 50, and 100 microg/ml of MGN for 30 min before exposure to 3 Gy of (60)Co gamma-radiation. The maximum decline in radiation-induced micronuclei was observed at a concentration of 50 microg/ml MGN; thereafter, a nonsignificant elevation in MNBNC frequency was observed at 100 microg/ml MGN. Since the lowest MNBNC frequency was observed for 50 microg/ml MGN, dose-response studies were undertaken using this concentration. Irradiation of HPBLs with 0, 1, 2, 3, or 4 Gy of gamma-radiation caused a dose-dependent elevation in the MNBNC frequency, while treatment of HPBLs with 50 microg/ml MGN 30 min before radiation resulted in significant declines in these frequencies. MGN alone did not alter the proliferation index. Irradiation caused a dose-dependent decline in the proliferation index, while treatment of HPBLs with 50 micro/ml MGN significantly elevated the proliferation index in irradiated cells. MGN treatment reduced hydrogen peroxide-induced lipid peroxidation in HPBLs in a concentration-dependent fashion. In cell-free studies, MGN inhibited the induction of (.)OH (hydroxyl), O(2) (.-) (superoxide), DPPH (1,1-diphenyl-2-picrylhydrazyl), and ABTS(.+) (2,2-azino-bis-3-ethyl benzothiazoline-6-sulphonic acid) radicals in a dose-dependent manner. The results of this study indicate that MGN possesses radioprotective properties by suppressing the effects of free radicals.

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“…The abrupt decline in MPCE frequency at 36 hours followed by its continued decrease at 48 hours post-irradiation is in accordance with earlier reports. 21,22,24,41,42 This may be due to the fact that micronuclei are formed in erythroblasts during mitosis. Erythropoiesis is an ongoing process, and there is a continual progression of cells from erythroblasts through the PCE stage to normochromatic erythrocytes (NCEs).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of radiation-induced clastogenicity by Aegle marmelos (L.) Correa in mice bone marrow exposed to different doses of γ-radiation

Jagetia

Venkatesh

2007

Hum Exp Toxicol

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The frequency of micronucleated polychromatic (MPCE), normochromatic erythrocytes (MNCE), and polychromatic/normochromatic erythrocyte ratio (PCE/NCE), was studied in the bone marrow of mice orally administered with 0, 200, 225, 250, 275 and 300 mg/kg body weight of hydroalcoholic leaf extract of Aegle marmelos (AME). Treatment of mice with AME, once daily for 5 consecutive days, before exposure to 2 Gy resulted in a significant decline in the frequency of MPCE when compared to the non-drug-treated irradiated control. The greatest reduction in MPCE was observed for 250 mg/kg body weight AME, accompanied by the highest polychromatic erythrocyte to normochromatic erythrocyte ratio, in comparison with the non-drug-treated irradiated control. Therefore, further studies were carried out using this dose of AME, where the animals were administered with 250 mg/kg body weight of AME before exposure to 0, 0.5, 1, 2, 3 and 4 Gy of γ-radiation and evaluated at 12, 24, 36 and 48 hours post-irradiation. Whole body irradiation of mice to different doses of γ-radiation resulted in a dose-dependent increase in the frequency of MPCE at all post-irradiation times. Treatment of 250 mg/kg AME orally (p.o.) before irradiation significantly reduced the frequency of MPCE at all post-treatment times. The frequency of MPCE increased with time, reached a peak level at 24 hours, and declined thereafter. The occurrence of MNCE has also shown a pattern similar to MPCE, except that the MNCE frequency reached a peak level by 48 hours. The AME significantly reduced the frequency of MNCE at all post-irradiation times, when compared to the non-drug-treated irradiated group. Treatment of mice with AME before exposure to different doses of γ-radiation resulted in the inhibition of a radiation-induced decline in the PCE/NCE ratio, when compared with the concurrent irradiated controls. To gain insight into the mechanism of action, AME was tested for its antioxidant effects in cell-free chemical systems using H2O 2/FeSO4 to generate hydroxyl (◦OH) radicals, which were measured by a fluorescent probe, 2V, 7V-dichlorofluorescin diacetate (DCFH/DA). Xanthine/xanthine oxidase was used to generate superoxide (O2◦-) anion radical, which was measured by a fluorescent probe dihydroethidium (DHE). AME significantly reduced fluorescence in a concentration dependent manner, indicating its efficacy to scavenge free radicals. Our results demonstrate that one of the mechanism of reduction in the radiation-induced DNA damage in mice bone marrow by AME may be due to scavenging of free radicals and elevation in the antioxidant status, as previously reported. Human & Experimental Toxicology (2007) 26, 111-124

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Teniposide (VM-26) treatment enhances the radiation-induced micronuclei in the bone marrow of mouse

Cited by 7 publications

References 33 publications

Modulation of Doxorubicin-Induced Genotoxicity byAegle marmelosin Mouse Bone Marrow: A Micronucleus Study

Modulation of Doxorubicin-Induced Genotoxicity byAegle marmelosin Mouse Bone Marrow: A Micronucleus Study

Effect of mangiferin on radiation-induced micronucleus formation in cultured human peripheral blood lymphocytes

Inhibition of radiation-induced clastogenicity by Aegle marmelos (L.) Correa in mice bone marrow exposed to different doses of γ-radiation

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