Induction of micronuclei in rat bone marrow and peripheral blood following acute and subchronic administration of azathioprine.
The frequency of micronuclei was assessed in polychromatic erythrocytes of bone marrow and in polychromatic and normochromatic erythrocytes in peripheral blood of rats following exposure to azathioprine for 28 days. This was compared with the incidence of micronuclei in bone-marrow following exposure to a single dose of azathioprine. The incidence of micronuclei in bone-marrow polychromatic erythrocytes at the maximum tolerated dose (10 mg/kg) following exposure for 28 days was 29.5/1000. The incidence of micronucleated polychromatic erythrocytes in the peripheral blood at this dose was 4.4/1000. At the maximum tolerated dose in the single-dose study (40 mg/kg) the incidence obtained at 48 h post-treatment was 15.7/1000. This supports the view that the use of animals in a subchronic toxicity study is at least as sensitive for assessing in vivo clastogenic activity as an acute study and could reduce animal usage in toxicology assessments.
Henderson
L
L
Environmental Safety Laboratory, Unilever Research, Colworth House, Sharnbrook, Bedfordshire, UK.
Fedyk
J
J
Windebank
S
S
Smith
M
M
D000818:Animals; D001379:Azathioprine / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects* / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects*; D015162:Micronucleus Tests; D051381:Rats; D017208:Rats, Wistar
D001379:Azathioprine