Micronuclei in adult and foetal mice exposed in vivo to heliotrine, urethane, monocrotaline and benzidine.
The level of clastogenic damage in mice following in vivo adult and transplacental exposure to benzidine, heliotrine, monocrotaline and urethane was compared using the micronucleus (MN) assays of polychromatic erythrocytes (PCE) found in mouse adult bone marrow and foetal liver. Saline was used as a negative control. Swiss-albino mice (gestation 17-19 days) were given a single acute intraperitoneal injection. Animals sacrificed 21 h after 0.75 LD50 of each chemical had significantly increased frequencies of micronucleated PCE in adult and foetal tissues (p < 0.05). Heliotrine resulted in the largest increases in mean value of micronucleated PCE, of 5.4% in adult bone marrow and 6.9% in foetal liver compared to control values of 0.7% and 0.9% for adult and foetal tissue respectively (p < 0.005). The induction of MN was significantly higher in foetal than adult cells for 0.75 LD50 monocrotaline and benzidine after 21 h (p < 0.0005), and for one LD50 heliotrine at 12, 24 and 30 h after injection in a time-response study (p < 0.02). Induction of MN following LD50 heliotrine showed peak MN expression in PCE at 18 h after injection for adult bone marrow (2.6%) and at 24 h for foetal liver (7.9%). The majority of micronucleated PCE in adult and foetal tissue contained only one MN (mean 74% in mice treated with chemicals and 91% in untreated mice). This study demonstrated the sensitivity of the transplacental MN assay for detecting clastogenic damage in mice induced by chemicals and their metabolites. The importance of monitoring indicators of toxicity was highlighted by changes in erythrocyte population composition and the presence of basophilic stippling following exposure to LD50 heliotrine.
Sanderson
B J
BJ
School of Biological Sciences, Flinders University of South Australia, Bedford Park.
Clark
A M
AM
D000818:Animals; D001560:Benzidines / Q000633:toxicity*; D001854:Bone Marrow Cells; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D007928:Lethal Dose 50; D008099:Liver / Q000196:embryology; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D015162:Micronucleus Tests; D016686:Monocrotaline / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*; D011247:Pregnancy; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity*; D014520:Urethane / Q000633:toxicity*
D001560:Benzidines; D009153:Mutagens; D011763:Pyrrolizidine Alkaloids; C029876:benzidine; D014520:Urethane; D016686:Monocrotaline; C010178:heliotrine