Todd L A, Bloom S E
Environ Mutagen. 1980;2(4):435-45. doi: 10.1002/em.2860020402.
To examine the development of drug-metabolizing enzyme systems in the early chick embryo, the procarcinogens, aflatoxin B1 (AF-B1) and 2-acetylamino-fluorene (2-AAF), and the direct-acting carcinogen, ethyl methanesulfonate (EMS) (positive control), were given to embryos; the sister-chromatid-exchange (SCE) technique was used as an indicator of conversion to active mutagenic metabolites. Chick embryos at two stages of incubation (3-day and 6-day) were exposed to the same graded series of dosages of the compounds for a period of 22 hours. All three mutagens increased the frequency of SCE above the control rate of 1,8 SCEs/cell. While a dose-dependent increase in SCE was obtained for both procarcinogens at each age, the mean SCE frequency was significantly higher in the 6-day embryos for each dosage given. In contrast, the direct-acting mutagen, EMS,. gave a reduced level of SCEs at the older age. These results suggest that the ability of early chick embryos to activate promutagens to forms capable of inducing SCE increases as development advances from three to six days of incubation (DI). In the 6-day embryo, the metabolic conversion is enhanced, resulting in a significant increase in the mutagenicity of the test chemicals.
为研究鸡胚早期药物代谢酶系统的发育情况,将致癌物前体黄曲霉毒素B1(AF - B1)、2 - 乙酰氨基芴(2 - AAF)以及直接作用致癌物甲磺酸乙酯(EMS)(阳性对照)给予胚胎;采用姐妹染色单体交换(SCE)技术作为转化为活性诱变代谢物的指标。处于两个孵化阶段(3日龄和6日龄)的鸡胚,在22小时内暴露于相同梯度系列剂量的化合物中。所有三种诱变剂均使SCE频率高于1.8次SCE/细胞的对照率。虽然在每个年龄段,两种致癌物前体的SCE均呈剂量依赖性增加,但对于每个给定剂量,6日龄胚胎的平均SCE频率显著更高。相比之下,直接作用诱变剂EMS在较老龄胚胎中导致SCE水平降低。这些结果表明,随着孵化从3天(DI)进展到6天,鸡胚早期将前诱变剂激活为能够诱导SCE的形式的能力增强。在6日龄胚胎中,代谢转化增强,导致测试化学品的诱变性显著增加。