The evaluation of a multiple dosing protocol for the mouse bone-marrow micronucleus assay using benzidine and 2,6-xylidine.
Male ICR mice were treated with 1, 2 or 3 daily doses of either benzidine or 2,6-xylidine. Groups of 5 animals were sacrificed 24 h after the last dose and the bone marrow examined for micronuclei. Benzidine was given at dose levels of 40 and 200 mg/kg and 2,6-xylidine was given at dose levels of 75 and 375 mg/kg. These doses represent 10 and 50% of the respective median lethal doses. Benzidine produced a significant (p less than 0.001) dose related increase in the incidence of micronucleated polychromatic erythrocytes (MPE), while 2,6-xylidine had no effect on the frequency of micronucleated cells. Statistical analyses of the data indicated that the incidence of MPE was independent of the number of doses administered prior to bone marrow harvest.
Parton
J W
JW
Lilly Research Laboratories, Division of Eli Lilly and Company, Greenfield, IN 46140.
Beyers
J E
JE
Garriott
M L
ML
Tamura
R N
RN
D000814:Aniline Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001560:Benzidines / Q000008:administration & dosage / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D003520:Cyclophosphamide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests / Q000379:methods; D009153:Mutagens / Q000494:pharmacology*; D012016:Reference Values
D000814:Aniline Compounds; D001560:Benzidines; D009153:Mutagens; C029876:benzidine; C007766:2,6-xylidine; D003520:Cyclophosphamide