Comparison of single-, double- or triple-exposure protocols for the rodent bone marrow/peripheral blood micronucleus assay using 4-aminobiphenyl and treosulphan.
Two human carcinogens, 4-aminobiphenyl (4AB) and treosulphan (Treo), were tested in male B6C3F1 mice for the induction of micronuclei in bone marrow and peripheral blood cells by 1-, 2- and 3-exposure protocols. Both compounds tested positive. The magnitude of response with respect to the incidence of micronucleated polychromatic erythrocytes by 2- and 3-exposure protocols was considerably higher than by the single-exposure protocol. The peripheral blood results for Treo were as typically seen with a 24-h delay when compared to the bone marrow. The peripheral blood results for 4AB, however, differed from those expected. The incidence of MN-PCE in peripheral blood of animals exposed to 4AB was significantly greater than seen in the bone marrow in 2- and 3-exposure protocols. There was also an increase in the % PCE at the 60 mg/kg dose level as a function of time. Based on these studies, it is concluded that a step-wise scoring scheme may be the best protocol for rodent micronucleus assay, involving a 3-exposure protocol with single sampling of bone marrow (24 h after the last treatment) and two samplings of peripheral blood (24 h and 48 h after the first treatment). This approach is cost-effective, it limits the number of animals required and provides maximum sensitivity.
Gulati
D K
DK
Environmental, Health Research and Testing, Inc., Lexington, KY 40503.
Wojciechowski
J P
JP
Kaur
P
P
D000611:Aminobiphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D002066:Busulfan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004912:Erythrocytes / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests / Q000379:methods
D000611:Aminobiphenyl Compounds; D002273:Carcinogens; C006757:4-biphenylamine; C018404:treosulfan; D002066:Busulfan