title: Induction of micronuclei in bone marrow of mice exposed to 1, 2 or 3 daily doses of urethane.
abstract: Urethane was studied for its potential to induce micronuclei in bone marrow of CD-1 mice following various dosing and sampling schedules. It was found that: (1) mice dosed for 3 days by gavage with urethane at daily doses of 300, 600 and 1200 mg.kg-1 showed no increases in micronuclei compared to normal control values; (2) mice injected with 3 daily intraperitoneal (i.p.) doses of urethane at 400 and 1200 mg.kg-1 demonstrated substantial and dose-related increases in micronuclei; (3) mice given urethane at i.p. doses of 400 mg.kg-1 for 1, 2 and 3 days showed protocol related micronucleus yields with triple greater than single greater than double dosing, while mice given urethane at i.p. doses of 1200 mg.kg-1 showed a different trend with double greater than single dosing, the triple-dosing regimen proving cytotoxic to the bone marrow; (4) mice exposed i.p. to 400 mg.kg-1 of urethane had more micronuclei when sampled at 24 h than at 48 h after 1 or 2 daily treatments, while mice dosed i.p. with 1200 mg.kg-1 of urethane showed more micronuclei at 48 h than at 24 h after a single treatment, the double-dosing protocol being toxic to the marrow; (5) female mice were more susceptible to bone-marrow micronucleus induction than males with both quantitative and qualitative sex differences noted, depending on dose, regimen and sample.
authors.affiliation: Inveresk Research International Ltd., Musselburgh, Scotland.
authors.forename: M
authors.initials: M
authors.lastname: Holmstrom
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004912:Erythrocytes / Q000187:drug effects* / Q000648:ultrastructure; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests / Q000379:methods; D012016:Reference Values; D012737:Sex Factors; D014520:Urethane / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D014520:Urethane