Gerharz C D, Gabbert H E, Engers R, Ramp U, Mayer H, Luley C
Department of Pathology, Johannes Gutenberg-University of Mainz, Federal Republic of Germany.
Br J Cancer. 1989 Oct;60(4):578-84. doi: 10.1038/bjc.1989.317.
The clonal rat rhabdomyosarcoma cell line BA-HAN-1C was tested for its susceptibility to differentiation induction with different polar compounds. This cell line is composed of proliferating mononuclear tumour cells, some of which spontaneously fuse to form terminally differentiated postmitotic myotube-like giant cells. Exposure of BA-HAN-1C cells to dimethylsulphoxide (DMSO), hexamethylene bisacetamide (HMBA), sodium butyrate (NaBut) and N-monomethylformamide (NMF) resulted in a significant inhibition of proliferation (P less than 0.001) and in a simultaneous increase in differentiation. The response was most pronounced after exposure to NMF as evidenced by a marked increase in the creatine kinase activity used as a biochemical marker of differentiation (P less than 0.05) and the number of terminally differentiated myotube-like giant cells (P less than 0.001). Furthermore, about 5% of the mononuclear cells exhibited thick and thin myofilaments which were never observed in the mononuclear cells of the control. In contrast, the effects of DMSO, HMBA and NaBut were exclusively confined to a significant increase in biochemical differentiation (P less than 0.05), whereas no increase in morphological differentiation was observed and the number of myotube-like giant cells even significantly (P less than 0.001) decreased. This heterogeneous response to differentiation induction with different polar compounds probably indicates different mechanisms of action and suggests that the induction of biochemical differentiation might be independently regulated from events leading to cell fusion and terminal differentiation.
对克隆大鼠横纹肌肉瘤细胞系BA-HAN-1C进行了测试,以检测其对不同极性化合物诱导分化的敏感性。该细胞系由增殖的单核肿瘤细胞组成,其中一些细胞会自发融合形成终末分化的有丝分裂后肌管样巨细胞。将BA-HAN-1C细胞暴露于二甲基亚砜(DMSO)、六亚甲基双乙酰胺(HMBA)、丁酸钠(NaBut)和N-单甲基甲酰胺(NMF)后,细胞增殖受到显著抑制(P<0.001),同时分化增加。暴露于NMF后的反应最为明显,这可通过用作分化生化标志物的肌酸激酶活性显著增加(P<0.05)以及终末分化的肌管样巨细胞数量增加(P<0.001)得到证明。此外,约5%的单核细胞表现出粗细肌丝,而在对照的单核细胞中从未观察到这种情况。相比之下,DMSO、HMBA和NaBut的作用仅局限于生化分化显著增加(P<0.05),而未观察到形态学分化增加,肌管样巨细胞数量甚至显著减少(P<0.001)。对不同极性化合物诱导分化的这种异质性反应可能表明作用机制不同,并提示生化分化的诱导可能与导致细胞融合和终末分化的事件独立调节。