KARYOTYPE OF MALIGNANT SKIN TUMORS OF TG.AC (ZETA-GLOBIN PROMOTED V-HA-RAS) MICE

恶性纤维肉瘤细胞的初步核型分析 早期传代培养的外植体提示非随机 6号和9号染色体获得和染色体丢失的非整倍体 13. 这些肿瘤细胞系在7至10天内100%诱导肿瘤。 同源宿主（10e5细胞/宿主，皮下）。 重新评估这些 使用改进的方法提高条带分辨率的细胞系 导致消除三体9和单体13下， 严格的评价条件，但指出，非随机 在6、10或15号染色体的获得中的非整倍体（10/14 纤维肉瘤和3/5的鳞状细胞癌）。大约50%的 观察到两种类型的肿瘤细胞系具有显著的 增加15三体。 没有显著的染色体异常， 在来自恶性肿瘤的有丝分裂细胞的剩余部分中观察到 在这种培养条件下， 这些观察结果 无论恶性肿瘤是否由化学物质引起， 促进（TPA或苯），非转基因FVB的DMBA/TPA处理， 或在老化丙酮处理对照中出现的罕见恶性肿瘤， 无论肿瘤被诊断为纤维肉瘤还是鳞状细胞癌， 癌 在早期传代培养中观察到的非整倍体 从TG. AC小鼠的恶性细胞可能代表克隆选择压力 和生长条件独立的关键遗传事件 参与肿瘤的发生和发展。 然而，这些数据在 与DMBA/TPA诱导鳞状细胞癌的范例形成鲜明对比， Sencar小鼠中的细胞癌，其中突变的c-Ha-ras、6三体和 7和c-Ha-ras等位基因失衡， 染色体7和11已经被描述。 额外的细胞核学和 需要进行分子遗传学研究来证实这些发现 并确定这种转基因小鼠模型是否是独一无二的， 肿瘤发生的替代途径是否参与了 皮下组织肉瘤或鳞状细胞癌的发展。

Initial karyotypic analysis of malignant fibrosarcoma tumor cells from explants in early passage secondary culture suggested non-random aneuploidy in the gain of a chromosome 6 and 9 and loss of chromosome 13. These tumor cell lines induced tumors in 7 to 10 days in 100% of syngeneic hosts (10e5 cells/host, subdermal). Re-evaluation of these cell lines using improved procedures to increase banding resolution resulted in the elimination of trisomy 9 and monosomy 13 under stringent evaluation conditions, but indicated that non-random aneuploidy in the gain of a chromosome 6, 10, or 15 (10/14 fibrosarcomas and 3/5 squamous cell carcinomas). Approximately 50% of the tumor cell lines of both types were observed with a significant increase in trisomy 15. No significant chromosomal abnormalities were observed in the remainder of the mitotic cells from malignant tumors observed under these culture conditions. These observations are consistent regardless of whether the malignancy resulted from chemical promotion (TPA or benzene), DMBA/TPA treatment of non-transgenic FVB, or rare malignancies arising in aging acetone treated controls and whether the tumors were diagnosed as fibrosarcomas or squamous cell carcinomas. The aneuploidy observed in early passage culture of malignant cells from TG.AC mice may represent clonal selection pressure and growth conditions independent of the critical genetic events involved in tumor initiation and promotion. However, these data are in distinct contrast to the paradigm of DMBA/TPA induction of squamous cell carcinomas in Sencar mice where mutated c-Ha-ras, trisomy 6 and 7, and allelic imbalance of c-Ha-ras, loss of heterozygosity on chromosome 7 and 11 have been described. Additional karyologic and molecular genetic studies will be required to corroborate these findings and determine whether this transgenic mouse model is unique and whether alternate pathways of tumorigenesis are involved in the development of sarcomas of the subcutis or squamous cell carcinomas.