Micronucleus induction by azobenzene and 1,2-dibromo-3-chloropropane in the rat: evaluation of a triple-dose protocol.
A triple-dose protocol was evaluated in the rat bone-marrow micronucleus test using azobenzene and 1,2-dibromo-3-chloropropane (DBCP) as test compounds. Dosing with 250 mg/kg azobenzene over 3 consecutive days led to an accumulation of micronucleated polychromatic erythrocytes. The magnitude of the effect was the same as that obtained after a single dose of 750 mg/kg in a previous study. In the single-dose study the effect was only detected at the 48 h sampling time. With the triple-dose protocol the effect was apparent 24 h after the last dose--thus eliminating the need for more than one sampling time. In the case of DBCP, the positive effect observed after a single dose diminished with increasing number of doses for the low dose but plateaued for the high dose, accompanied by a marked cytotoxic effect. It is therefore concluded, that for one of the compounds, azobenzene, the triple-dose protocol provided an advantage whereas for the other, DBCP, it failed to do so and led to results which are rather difficult to interpret. Furthermore, the number of animals necessary to select an appropriate dose level appears to be higher than in the single-dose protocol.
George
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Genetic and Reproductive Toxicology Department, Glaxo Group Research, Ware, Great Britain.
Wootton
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Gatehouse
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D000818:Animals; D001391:Azo Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004912:Erythrocytes / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests / Q000379:methods; D009153:Mutagens / Q000494:pharmacology*; D011407:Propane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001391:Azo Compounds; D009153:Mutagens; C007318:1,2-dibromo-3-chloropropane; C009850:azobenzene; D011407:Propane