Director A E, Nath J, Ramsey M J, Swiger R R, Tucker J D
Genetics and Developmental Biology Program, College of Agriculture and Forestry, West Virginia University, Morgantown 26506-6108, USA.
Mutat Res. 1996 Jan 16;359(1):53-61. doi: 10.1016/s0165-1161(96)90009-6.
The cytogenetic effects in mice chronically fed the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5b]pyridine (PhIP) were evaluated by chromosome painting, micronucleated normochromatic erythrocytes (MN NCEs) and sister chromatid exchanges (SCEs). PhIP and numerous other heterocyclic amines have been isolated from cooked foods, and many have been found to be carcinogenic in laboratory rodents. Female C57BL/6N mice were chronically fed a diet containing 0, 100, 250 or 400 ppm of PhIP beginning at 8 weeks of age. Peripheral blood and bone marrow were taken from 5 mice per treatment group at 1, 4 and 6 months from the start of exposure. PhIP was removed from the diet for a final month of the experiment, at which time blood was taken from the remaining animals. Chromosome-specific composite DNA probes for mouse chromosomes 2 and 8 were hybridized to metaphase cells from each tissue. The 1- and 4-month time points showed no statistically significant difference between the control and exposed mice for either tissue in chromosome aberration frequencies. Both MN NCEs and SCEs were analyzed at a single time point during exposure (4 months for MN NCEs and 6 months for SCEs) and again 1 month after removing PhIP from the diet. MN NCEs in the peripheral blood showed a statistically significant dose response, with all values decreasing significantly 1 month after removing PhIP from the diet. SCE frequencies in the peripheral blood showed an approximate doubling compared to control mice, and decreased to control levels 1 month after removing PhIP from the diet. SCE frequencies in the bone marrow of exposed mice showed no difference from the control animals. These results show that chronic ingestion of PhIP by female C57BL/6 mice does not produce persistent cytogenetic damage as visualized by chromosome aberrations, MN NCEs or SCEs.
通过染色体涂染、微核正染红细胞（MN NCEs）和姐妹染色单体交换（SCEs）评估长期喂食杂环胺2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶（PhIP）的小鼠的细胞遗传学效应。PhIP和许多其他杂环胺已从熟食中分离出来，并且许多已被发现在实验啮齿动物中具有致癌性。从8周龄开始，对雌性C57BL/6N小鼠长期喂食含有0、100、250或400 ppm PhIP的饮食。在暴露开始后的1、4和6个月，从每个处理组的5只小鼠中采集外周血和骨髓。在实验的最后一个月，从饮食中去除PhIP，此时从剩余动物中采集血液。用于小鼠2号和8号染色体的染色体特异性复合DNA探针与来自每个组织的中期细胞杂交。在1个月和4个月的时间点，对照小鼠和暴露小鼠的任一组织在染色体畸变频率上均无统计学显著差异。在暴露期间的单个时间点（MN NCEs为4个月，SCEs为6个月）以及从饮食中去除PhIP 1个月后，对MN NCEs和SCEs进行了分析。外周血中的MN NCEs显示出统计学显著的剂量反应，从饮食中去除PhIP 1个月后，所有值均显著下降。外周血中的SCE频率与对照小鼠相比大约增加了一倍，并且从饮食中去除PhIP 1个月后降至对照水平。暴露小鼠骨髓中的SCE频率与对照动物无差异。这些结果表明，雌性C57BL/6小鼠长期摄入PhIP不会产生如染色体畸变、MN NCEs或SCEs所显示的持续性细胞遗传学损伤。
