IN VIVO MUTAGENICITY/CARCINOGENICITY OF HETEROCYCLIC AMINES IN TRANSGENIC MICE

熟肉制品的体内致突变性和肝癌性 衍生的杂环胺2-氨基-3，8-二甲基咪唑并[4，5-f]喹喔啉 在MutaMice（携带lacZ的转基因小鼠）中检查了MeIQx 突变报告基因。探讨c-myc基因过表达对乳腺癌细胞增殖的影响 对MeIQx诱导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。小鼠 在饲料中添加MeIQx（0.06%），持续30和40周。DNA加合物 通过32 P-后标记测量形成并检查诱变 在lacZ基因中。MeIQx-DNA加合物水平在c-myc 转基因小鼠比不携带这种转基因的小鼠。c-Myc 过表达增加了MeIQx诱导的肝肿瘤的发生率 并增加了lacZ基因的突变频率。结果支持 c-myc癌基因的过度表达促进MeIQx的概念- 肝癌发生，部分通过诱变机制。

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.