Sanderson B J, Clark A M
School of Biological Sciences, Flinders University of South Australia, Bedford Park.
Mutat Res. 1993 Jan;285(1):27-33. doi: 10.1016/0027-5107(93)90048-k.
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.
使用小鼠成年骨髓和胎儿肝脏中多染性红细胞（PCE）的微核（MN）试验，比较了成年小鼠体内和经胎盘暴露于联苯胺、天芥菜碱、野百合碱和氨基甲酸乙酯后产生的致断裂损伤水平。以生理盐水作为阴性对照。对瑞士白化小鼠（妊娠17 - 19天）进行单次急性腹腔注射。在给予每种化学物质0.75 LD50后21小时处死动物，成年和胎儿组织中微核化PCE的频率显著增加（p < 0.05）。天芥菜碱导致微核化PCE的平均值增加幅度最大，成年骨髓中增加了5.4%，胎儿肝脏中增加了6.9%，而成年和胎儿组织的对照值分别为0.7%和0.9%（p < 0.005）。在21小时后，对于0.75 LD50的野百合碱和联苯胺，胎儿细胞中微核的诱导显著高于成年细胞（p < 0.0005）；在一项时间反应研究中，注射后12、24和30小时，对于1 LD50的天芥菜碱，胎儿细胞中微核的诱导也显著高于成年细胞（p < 0.02）。给予LD50天芥菜碱后微核的诱导显示，成年骨髓中PCE在注射后18小时微核表达达到峰值（2.6%），胎儿肝脏在24小时达到峰值（7.9%）。成年和胎儿组织中大多数微核化PCE仅含有一个微核（化学物质处理的小鼠平均为74%，未处理的小鼠为91%）。本研究证明了经胎盘微核试验对于检测化学物质及其代谢产物诱导的小鼠致断裂损伤的敏感性。暴露于LD50天芥菜碱后红细胞群体组成的变化和嗜碱性点彩的出现突出了监测毒性指标的重要性。
