Balansky R, Blagoeva P, Mircheva Z
Laboratory of Chemical Mutagenesis and Carcinogenesis, National Centre of Oncology, Sofia, Bulgaria.
Mutat Res. 1992 Feb;281(2):99-103. doi: 10.1016/0165-7992(92)90043-h.
Single intraperitoneal (i.p.) treatment of male and female BDF1 (C57B1 x DBA2) mice with urethane (0.5 or 1.0 g/kg) caused a significant increase in micronucleated polychromatic erythrocytes (MNPCE) in bone marrow after 24 h. The clastogenic effect observed was dose-, sex- and age-dependent, the male and younger (6-8 weeks old) animals being more susceptible than the female and older (6 months of age) mice. 3-week oral treatment of female Balb/c mice with urethane (3 g/l added to the drinking water) caused an up to 4-fold increase in the number of micronucleated normochromatic erythrocytes (MNNCE) in mouse peripheral blood. In a month after the carcinogen treatment was stopped, the number of MNNCE dropped to the control values. In addition, a single i.p. treatment of pregnant BDF1 mice on day 17 of gestation with urethane (1.0 g/kg) caused a 514.3% (p less than 0.001) elevation of MNPCE in mouse fetal liver after 24 h as well as a 154.4% (p less than 0.05) increase in MNPCE frequency in the fetal peripheral blood. At this time point, the clastogenic response in mouse fetal liver erythroblasts was less pronounced than that detected in the maternal bone marrow cells. Urethane is a strong clastogen in mice when administered either intraperitoneally or orally and the micronucleus test applied to adult and fetal erythroblasts is a convenient method of choice for studying the acute and subchronic clastogenicity of this carcinogen, its transplacental effects as well as the influence of modifying factors on these processes.
用乌拉坦（0.5或1.0克/千克）对雄性和雌性BDF1（C57B1×DBA2）小鼠进行单次腹腔注射后24小时，骨髓中微核多染性红细胞（MNPCE）显著增加。观察到的致断裂效应具有剂量、性别和年龄依赖性，雄性和年轻（6 - 8周龄）动物比雌性和年长（6月龄）小鼠更敏感。用乌拉坦（添加到饮用水中，浓度为3克/升）对雌性Balb/c小鼠进行为期3周的口服处理，导致小鼠外周血中微核正染性红细胞（MNNCE）数量增加高达4倍。在停止致癌物处理一个月后，MNNCE数量降至对照值。此外，在妊娠第17天对怀孕的BDF1小鼠进行单次腹腔注射乌拉坦（1.0克/千克），24小时后小鼠胎儿肝脏中的MNPCE升高了514.3%（p小于0.001），胎儿外周血中MNPCE频率增加了154.4%（p小于0.05）。此时，小鼠胎儿肝脏成红细胞中的致断裂反应不如母体骨髓细胞中明显。乌拉坦经腹腔或口服给药时在小鼠中是一种强致断裂剂，应用于成年和胎儿成红细胞的微核试验是研究这种致癌物的急性和亚慢性致断裂性、其经胎盘效应以及修饰因子对这些过程影响的一种方便的选择方法。
