Genotoxicity of compounds from cooked beef in repair-deficient CHO cells versus Salmonella mutagenicity.
Genotoxicity of compounds from cooked beef in repair-deficient CHO cells versus Salmonella mutagenicity.
复制标题
修复缺陷 CHO 细胞中熟牛肉化合物的基因毒性与沙门氏菌致突变性。
DOI：
10.1093/mutage/2.6.483
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发表时间：
1987
期刊：
影响因子：
2.7
通讯作者：
J. S. Felton
中科院分区：
文献类型：
--
作者：
L. H. Thompson;James D. Tucker;S. Stewart;Mari Christensen;Edmund P. Salazar;A. Carrano;J. S. Felton
此前，在Ames/沙门氏菌还原试验中分离出的一系列化合物在油炸牛肉中被发现，并进行了化学合成以进行进一步评价。本研究检测了三种化合物对缺乏核苷酸切除修复的中国仓鼠卵巢（CHO）细胞UV5系的遗传毒性作用。2-氨基-3,4-二甲基-咪唑[4,5-f]喹啉（MeIQ）和2-氨基-3,8-二甲基-咪唑[4,5-f]喹诺啉（MeIQx）对细胞杀伤、诱导hprt突变和姐妹染色单体交换均有很弱的反应。这些效应发生在100-800微克/毫升（大约溶解度极限）的剂量范围内，并且没有观察到剂量依赖性增加。两种化合物均未诱导染色体畸变。这些化合物在正常CHO细胞和UV5细胞中也没有产生不同的细胞毒性，这表明潜在的可修复DNA损伤不是观察到的细胞杀伤的原因。与这些结果相反，占牛肉细菌诱变剂质量90%以上的2-氨基-1-甲基-6-苯基咪唑[4,5-b]吡啶（PhIP）在1-3微克/毫升剂量范围内的所有终点均呈强烈阳性。PhIP还具有明显的细胞毒性差异（比率为6）和细胞存活曲线，这些曲线强烈依赖于修复能力。由于PhIP在沙门氏菌TA1538中的诱变性比MeIQ和MeIQx低50到300倍，这些结果表明，就这些与食物有关的化合物的相对效力而言，细菌和哺乳动物的测定存在重大差异。
A series of compounds isolated on the basis of their mutagenicity in the Ames/Salmonella reversion assay were previously identified in fried beef and chemically synthesized for further evaluation. In this study three of these compounds were tested for genotoxic effects in the UV5 line of Chinese hamster ovary (CHO) cells, which is deficient in nucleotide excision repair. Both 2-amino-3,4-dimethyl-imidazo]4,5-f]quinoline (MeIQ) and 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx) gave very weak responses for cell killing, hprt mutation induction and sister chromatid exchange. These effects occurred at doses in the range of 100-800 micrograms/ml (approximately solubility limit), and dose-dependent increases were not observed. Induction of chromosomal aberrations did not occur with either compound. Nor did either of these compounds produce differential cytotoxicity in normal CHO cells versus UV5 cells, indicating that potentially repairable DNA damage was not responsible for the observed cell killing. In contrast to these results, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP), which constitutes greater than 90% of the mass of bacterial mutagens in beef, was strongly positive for all endpoints at doses in the range 1-3 micrograms/ml. PhIP also gave marked differential cytotoxicity (ratio of 6) and cell survival curves that were strongly dependent on repair capacity. Because PhIP is 50- to 300-fold less mutagenic than MeIQ and MeIQx in Salmonella TA1538, these results point to major differences between the bacterial and mammalian assays in terms of the relative potency of these food-related compounds.