Donnelly P J, Massey T E
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.
Mol Carcinog. 1999 Sep;26(1):62-7. doi: 10.1002/(sici)1098-2744(199909)26:1<62::aid-mc8>3.0.co;2-u.
Lung cells isolated from AC3F1 (A/J x C3H/HeJ) mice 7 wk after treatment with the carcinogenic mycotoxin aflatoxin B1 (AFB1) were examined for point mutations in the Ki-ras oncogene. Ki-ras mutant allele frequencies in fractions enriched with nonciliated bronchiolar epithelial (Clara) cells were consistently higher than in alveolar type II cell fractions. Mutant alleles were undetectable or minimal in macrophage- and polymorphonuclear leukocyte-enriched fractions. In cells from vehicle (dimethyl sulfoxide)-treated mice, small proportions of mutant Ki-ras alleles were found in the Clara cell-enriched fraction but not in other cell fractions. The results indicated that Clara cells are particularly susceptible to AFB1-induced Ki-ras mutation, an early event in AFB1-induced mouse lung tumorigenesis.
在用致癌霉菌毒素黄曲霉毒素B1（AFB1）处理7周后，从AC3F1（A/J×C3H/HeJ）小鼠分离出的肺细胞被检测Ki-ras癌基因中的点突变。富含无纤毛细支气管上皮（克拉拉）细胞的组分中的Ki-ras突变等位基因频率始终高于肺泡II型细胞组分中的频率。在富含巨噬细胞和多形核白细胞的组分中未检测到或仅有少量突变等位基因。在用载体（二甲基亚砜）处理的小鼠的细胞中，在富含克拉拉细胞的组分中发现了少量突变的Ki-ras等位基因，但在其他细胞组分中未发现。结果表明，克拉拉细胞对AFB1诱导的Ki-ras突变特别敏感，这是AFB1诱导的小鼠肺癌发生中的早期事件。
