Aso H, Shibuya E, Suzuki F, Nakamura T, Inoue H, Ebina T, Ishida N
Gan To Kagaku Ryoho. 1985 Dec;12(12):2345-51.
The antitumor effect of an organic germanium compound, carboxyethylgermanium sesquioxide (Ge-132), was examined in mice using two systems: one, the ascitic form of Ehrlich carcinoma in DDI mice, and the other, the solid form of Meth-A fibrosarcoma in BALB/c mice. In the mice with Ehrlich ascitic tumors, a remarkable prolongation in life span was observed after intraperitoneal (i.p.) or per oral (p.o.) administration of Ge-132 (300 mg/kg), but not after intravenous (i.v.) injection of the same compound. Following i.p. or p.o. administration, cytotoxic macrophages (Mø) were induced in the peritoneal cavity after 48 h. although this was not the case after i.v. injections. When the in vivo effect of these in vitro active Mø was examined after adoptive transfer to mice bearing Ehrlich ascitic tumor cells, a significant antitumor effect was noted. In the mice bearing solid Meth-A tumors, i.v. injections of Ge-132 (100 mg/kg) were found to inhibit tumor growth remarkably, although i.p. and p.o. administrations did not have the same result. This inhibitory effect of Ge-132 by i.v. administration was explained by the continued augmentation of NK activity in peripheral blood, which was followed by the induction of specific killer cells appearing in the spleen. When the mice which had recovered from Meth-A tumor growth, following i.v. injections of Ge-132, were challenged with the same tumor on day 30, all mice were able to tolerate the challenge, but not a challenge of RL male 1 tumor cells. These observations may indicate that the differing antitumor effects of Ge-132 produced when different administration methods are used can be explained by the variation in effector cells induced by such different administration routes.
使用两种系统在小鼠中检测了有机锗化合物羧乙基锗倍半氧化物(Ge-132)的抗肿瘤作用:一种是DDI小鼠中的艾氏腹水癌腹水形式,另一种是BALB/c小鼠中的Meth-A纤维肉瘤实体形式。在患有艾氏腹水瘤的小鼠中,腹腔内(i.p.)或口服(p.o.)给予Ge-132(300mg/kg)后观察到寿命显著延长,但静脉内(i.v.)注射相同化合物后未观察到这种情况。腹腔内或口服给药后,48小时后腹腔内诱导出细胞毒性巨噬细胞(Mø),但静脉内注射后并非如此。当将这些体外活性Mø过继转移到携带艾氏腹水瘤细胞的小鼠中后检测其体内效应时,发现有显著的抗肿瘤作用。在患有实体Meth-A肿瘤的小鼠中,发现静脉内注射Ge-132(100mg/kg)可显著抑制肿瘤生长,尽管腹腔内和口服给药没有相同的结果。静脉内给药的Ge-132的这种抑制作用可通过外周血中NK活性的持续增强来解释,随后脾脏中出现特异性杀伤细胞。当在静脉内注射Ge-132后从Meth-A肿瘤生长中恢复的小鼠在第30天用相同肿瘤进行攻击时,所有小鼠都能够耐受攻击,但不能耐受RL雄性1肿瘤细胞的攻击。这些观察结果可能表明,使用不同给药方法时产生的Ge-132不同抗肿瘤作用可通过这种不同给药途径诱导的效应细胞的变化来解释。