Isolation of a nontoxic lipid A fraction containing tumor regression activity.
Isolation of a nontoxic lipid A fraction containing tumor regression activity.
复制标题
分离出具有肿瘤消退活性的无毒脂质 A 级分。
作者：
K. Takayama;E. Ribi;J. Cantrell
从鼠伤寒沙门氏菌无庚糖突变体中获得的galanos型内毒素经pH为4.5的醋酸钠在100度下处理两个循环后转化为脂质A，并在deae -纤维素柱上分离成几个部分（部分III至部分VII）。对菌株2豚鼠和同基因系10肝细胞癌的肿瘤消退研究表明，当与海藻糖二真菌酸酯和额外的肿瘤消退因子（以前指定为ACP）联合并加入油滴时，所有部分都有效（治愈率为78%至100%）。与未分离的脂质A （CELD50为0.0546微克，FI40为0.046微克）相比，低极性组分（IV组分）相对无毒[接种于11日龄小鸡胚胎的中致死剂量（CELD50）大于10微克]和无热原性[在1小时和1度时家兔发烧指数（发烧曲线下面积）估计为40平方厘米的剂量（FI40为5微克）]。其余部分与n -乙酰muramyl- l- seryl- d -异谷氨酰胺联合静脉注射豚鼠均有毒性和热原性，可引起严重的内毒素休克。IV组分加n -乙酰muramyl- l- seryl- d -异谷氨酰胺不会引起内源性休克。IV馏分的磷酸盐含量约为有毒馏分的一半。
Galanos-type endotoxin obtained from the heptose-less mutant of Salmonella typhimurium was converted to Lipid A by two cycles of treatment with sodium acetate, pH 4.5, at 100 degrees and separated on a DEAE-cellulose column into several fractions (Fractions III to VII). Tumor regression studies with strain 2 guinea pigs and syngeneic line 10 hepatocellular carcinoma showed that all fractions were effective when combined with trehalose dimycolates and an additional tumor regression factor (previously designated ACP) and incorporated into oil droplets (78 to 100% cures). A low polar fraction (Fraction IV) was relatively nontoxic [the medium lethal dose for 11-day-old chick embryos inoculated i.v. (CELD50) was more than 10 micrograms] and nonpyrogenic [the dose estimated to give a fever index (area under fever curve) of 40 sq cm in rabbits when 1 hr and 1 degrees are plotted as 1 (FI40) was 5 micrograms] as compared to the unfractionated Lipid A (CELD50 of 0.0546 micrograms; FI40 of 0.046 micrograms). All other fractions were toxic and pyrogenic and caused severe endotoxic shocks when combined with N-acetylmuramyl-L-seryl-D-isoglutamine and injected i.v. into guinea pigs. Fraction IV plus N-acetylmuramyl-L-seryl-D-isoglutamine did not cause endotoxic shock. The phosphate content of Fraction IV was about one-half of that detected in the toxic fractions.