Document Detail


Radioprotective effects of DNA ligands Hoechst-33342 and 33258 in whole body irradiated mice.
MedLine Citation:
PMID:  9717448     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Radioprotective effects of bisbenzimidole derived DNA ligands Hoechst-33342 (H-342) and Hoechst-33258 (H-258) have been investigated in whole body irradiated stain-A and Balb/c mice (Co-60 Gamma-ray, absorbed doses of 2.5 to 10 Gy delivered at dose rates of 0.01 to 0.50 Gy/min). Biodistribution of Hoechst dyes (2 or 5 mg/kg, body wt., i.v.) and their effects on cell cycle kinetics in bone marrow were studied by flow cytometry. Protection against radiation-induced chromosomal aberrations, micronuclei formation, alterations in DNA content dispersion, inhibition of erythropoiesis and animal lethality were investigated. Significant amount of DNA bound Hoechst could be observed in liver, intestine, kidney and brain for more than 14 days after its administration, while in the bone marrow cells, a reduction in the bound Hoechst was noticed after 7 days. H-342 significantly reduced the radiation-induced chromosome aberrations mainly due to a decrease in the frequency of acentrics (nearly 30%), while a marginal decrease (10%) in the dicentrics was observed at all the dose rates studied. Both H-342 and H-258 reduced the radiation-induced micronuclei formation in a dose dependent manner (2-10 mg/kg body wt.) and this protective effect was observed up to 6 days after the administration. Neither of the two compounds induced any cytogenetic damage in the bone marrow cells of unirradiated animals nor induced tumours at the doses used here (< 5 mg/kg, body wt. i.v.). Reduction in cytogenetic damage of bone marrow cells led to a faster recovery of erythropoesis as observed by increased PCE/NCE ratio in the peripheral blood erythrocytes of the animals which received Hoechst before irradiation. H-258 (5 mg/kg body wt.) given 18 hr before irradiation reduced radiation-induced animal death (5-9 Gy), while no significant effect was observed at higher doses (10 Gy). However, H-342, which has a higher cell permeability, even at a lower dose (2 mg/kg body wt.) showed significant protection at 10 Gy. The protective effects could be enhanced further, by combining these DNA binding agents with the glucose analogue, 2-deoxy-D-glucose (2-DG) which has been shown earlier to protect bone marrow cells against radiation damage.
Authors:
S P Singh; V R Jayanth; S Chandna; B S Dwarakanath; S Singh; J S Adhikari; V Jain
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Indian journal of experimental biology     Volume:  36     ISSN:  0019-5189     ISO Abbreviation:  Indian J. Exp. Biol.     Publication Date:  1998 Apr 
Date Detail:
Created Date:  1998-09-18     Completed Date:  1998-09-18     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0233411     Medline TA:  Indian J Exp Biol     Country:  INDIA    
Other Details:
Languages:  eng     Pagination:  375-84     Citation Subset:  IM    
Affiliation:
Institute of Nuclear Medicine and Allied Sciences, Lucknow Marg, Delhi, India.
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MeSH Terms
Descriptor/Qualifier:
Animals
Benzimidazoles / pharmacology,  therapeutic use*
Bisbenzimidazole / pharmacology,  therapeutic use*
DNA / drug effects*
Mice
Mice, Inbred BALB C
Radiation Injuries, Experimental / prevention & control*
Radiation-Protective Agents / therapeutic use*
Whole-Body Irradiation
Chemical
Reg. No./Substance:
0/Benzimidazoles; 0/Radiation-Protective Agents; 23491-44-3/Bisbenzimidazole; 23491-52-3/HOE 33342; 9007-49-2/DNA

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