Chromosomal composition of micronuclei in mouse bone marrow treated with rifampicin and nicotine, analyzed by multicolor fluorescence in situ hybridization with pancentromeric DNA probe.
The mechanism underlying the induction of micronuclei induced by rifampicin and nicotine in mouse bone marrow was investigated by fluorescence in situ hybridization assay using mouse minor satellite DNA probe. Colchicine and mitomycin, known to be predominantly clastogenic and aneugenic, respectively were used as positive controls and these compounds produced the expected responses. In animals treated with different doses of rifampicin (10-320 mg/kg), the frequencies of micronucleated polychromatic erythrocytes (MNPCE) increased significantly after treatment with 160 and 320 mg/kg. Furthermore, rifampicin caused a significant depression of erythroblast proliferation at the high dose. At the two highest doses of 160 and 320 mg/kg rifampicin, a total of 0.96% and 1.44% MNPCE, respectively were found. Of the rifampicin-induced signal-positive MNPCE, an average of 58.1% of them was centromere-negative, reflecting the clastogenic activity of rifampicin. Correspondingly, about 41.9% of induced MNPCE were centromere-positive, representing the aneugenic activity of rifampicin. Eight and 16 mg/kg of nicotine induced 0.84% and 1.2% MNPCE, respectively, and of these an average of 29.5% showed one or more fluorescent signals, reflecting the predominant clastogenic activity of nicotine. The results obtained demonstrate that rifampicin induced both chromosome breakage and numerical chromosomal abnormalities, whereas nicotine induced one type of MNPCE and it could be considered a clastogenic agent.
Attia
Sabry M
SM
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt. attiasm@yahoo.com
D000284:Administration, Oral; D024422:Aneugens / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000473:pathology; D015342:DNA Probes; D004305:Dose-Response Relationship, Drug; D004900:Erythroblasts / Q000187:drug effects / Q000473:pathology; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests / Q000379:methods*; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D009538:Nicotine / Q000008:administration & dosage / Q000633:toxicity*; D015203:Reproducibility of Results; D012293:Rifampin / Q000008:administration & dosage / Q000633:toxicity*
D024422:Aneugens; D015342:DNA Probes; D009153:Mutagens; D009538:Nicotine; D012293:Rifampin