IN VIVO MUTAGENICITY/CARCINOGENICITY OF HETEROCYCLIC AMINES IN TRANSGENIC MICE

熟肉的体内致突变性和致癌性 衍生杂环胺2-氨基-3，8-二甲基咪唑并[4，5-f]喹恶啉 (MeIQx)在携带LacZ的转基因小鼠MutaMice中进行了检测 突变的报告基因。评价c-myc基因过表达的影响 关于MeIQx的致突变性和致癌性，MutaMice进一步 与c-myc转基因小鼠(白蛋白启动子/增强子)杂交。老鼠 日粮中添加0.06%的MeIQx，饲喂30周和40周。DNA加合物 用~(32)P-后标记测量形成，并检测诱变 在LacZ基因中。C-myc中MeIQx-DNA加合物水平较高 转基因小鼠比没有携带这种转基因的小鼠。C-myc 过表达增加MeIQx诱导的肝肿瘤的发生率 提高了LacZ基因的突变频率。结果是支持的 C-myc癌基因的过度表达促进MeIQx- 肝癌的发生在一定程度上是通过诱变机制实现的。

The in vivo mutagenicity and hepatocarcinogenicity of the cooked-meat derived heterocyclic amine 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)was examined in MutaMice, transgenic mice carrying the lacZ mutational reporter gene. To evaluate the effect of c-myc overexpression on MeIQx-induced mutagenicity and carcinogenicity, MutaMice were further crossed with c-myc transgenic mice (albumin promoter/enhancer). Mice were fed MeIQx in the diet (0.06%) for 30 and 40 weeks. DNA adduct formation was measured by 32P-postlabeling and mutagenesis was examined in the lacZ gene. MeIQx-DNA adduct levels were higher in c-myc transgenic mice than in mice not carrying this transgene. C-myc overexpression increased the frequency of MeIQx-induced hepatic tumors and increased the mutant frequency in the lacZ gene. The results support the notion that overexpression of the c-myc oncogene promotes MeIQx- hepatocarcinogenesis, in part, via a mutagenic mechanism.