Bose K K, Zahurak M L, Allison D C
Department of Surgery, Medical College of Ohio, Toledo 43699-0008, USA.
Cell Prolif. 1995 Jul;28(7):403-14. doi: 10.1111/j.1365-2184.1995.tb00081.x.
We analysed the effects of nitrogen mustard (HN2) on the growth, cell cycle distributions, and ratios of tumour cells to host cells for MCa-11 tumours grown in vivo. Treatment of tumour-bearing BALB/c mice with 3 mg/kg of HN2 produced a significant slowing of MCa-11 tumour growth. Seventy-two hours after treatment in vivo with either 3 or 4 mg/kg of HN2, the host cells in the treated tumours showed a significantly decreased G0/G1 peak and an increased G2/M peak (P < 0.01), whereas the cancer cells in the treated tumours showed significant increases in the G0/G1 peak coupled with relatively decreased proportions of S and G2/M tumour cells (P < 0.001). The ratio of the total number of cancer cells to the total number of host cells in the tumours was significantly increased 72 h after HN2 administration (P < 0.01). Thirty-two days after treatment with HN2, the cell cycle distributions of the host and tumour cells in the treatment and control tumours had returned to being identical, but the ratio of the total number of cancer cells to the total number of host cells remained increased in the treated tumours (P < 0.01). These results show that the administration in vivo of HN2 can lead to entirely different cell cycle effects for the host and cancer cells in the same tumour, and that the partial growth arrest of MCa-11 tumours from HN2 treatment may be due in part to the preferential destruction of host cells rather than solely to a direct cytotoxic effect on the cancer cells.
我们分析了氮芥(HN2)对体内生长的MCa - 11肿瘤的生长、细胞周期分布以及肿瘤细胞与宿主细胞比例的影响。用3mg/kg的HN2处理荷瘤BALB/c小鼠,可显著减缓MCa - 11肿瘤的生长。在用3mg/kg或4mg/kg的HN2进行体内处理72小时后,处理过的肿瘤中的宿主细胞显示G0/G1峰显著降低,G2/M峰升高(P < 0.01),而处理过的肿瘤中的癌细胞显示G0/G1峰显著增加,同时S期和G2/M期肿瘤细胞的比例相对降低(P < 0.001)。在给予HN2 72小时后,肿瘤中癌细胞总数与宿主细胞总数的比例显著增加(P < 0.01)。用HN2处理32天后,处理组和对照组肿瘤中宿主细胞和肿瘤细胞的细胞周期分布恢复相同,但处理过的肿瘤中癌细胞总数与宿主细胞总数的比例仍然增加(P < 0.01)。这些结果表明,体内给予HN2可导致同一肿瘤中宿主细胞和癌细胞产生完全不同的细胞周期效应,并且HN2处理导致MCa - 11肿瘤部分生长停滞可能部分归因于宿主细胞的优先破坏,而非仅仅是对癌细胞的直接细胞毒性作用。