咖啡因的一种尿嘧啶代谢物6-氨基-5-甲酰基-甲基氨基-1,3-二甲基尿嘧啶的体外和体内细胞毒性

In vitro and in vivo cytotoxicity of 6 amino-5-formyl-methylamino-1,3-dimethyl uracil, a uracilic metabolite of caffeine.

作者信息

Garattini S, Erba E, Morasca L, Peri G, Mantovani A, Filippeschi S, Spreafico F, Arnaud M

出版信息

Toxicol Lett. 1982 Feb;10(2-3):313-9. doi: 10.1016/0378-4274(82)90094-7.

Abstract

The in vitro cytotoxicity of 6 amino-5 formylmethylamino-1,3 dimethyluracil (ADMU) a major metabolite of caffeine in rats was studied by cell counts or [3H]thymidine incorporation in the murine Lewis lung carcinoma (3LL) and L929 fibroblast cells and in the human E cell line derived from an ovarian carcinoma. Unlike 5-fluorouracil (5FU) which was markedly cytotoxic, ADMU concentrations up to 60 micrograms/ml were devoid appreciable cytocidal action. Similarly, 1-10 micrograms 5FU markedly inhibited the blastogenic response of rat lymphocytes to PHA, whereas lymphoproliferation was not affected at ADMU concentrations up to 100 micrograms/ml. In vivo administration of ADMU (40 mg/kg, twice a day on day 1 to 3) to L1210 leukaemia-bearing mice caused a transient short-lasting reduction of tumour cell numbers only on day 6 after leukaemia inoculation.U

摘要

通过细胞计数或[3H]胸苷掺入法，在小鼠Lewis肺癌（3LL）细胞、L929成纤维细胞以及源自卵巢癌的人E细胞系中，研究了咖啡因在大鼠体内的主要代谢产物6-氨基-5-甲酰甲基氨基-1,3-二甲基尿嘧啶（ADMU）的体外细胞毒性。与具有明显细胞毒性的5-氟尿嘧啶（5FU）不同，高达60微克/毫升的ADMU浓度没有明显的杀细胞作用。同样，1-10微克的5FU显著抑制大鼠淋巴细胞对PHA的增殖反应，而在高达100微克/毫升的ADMU浓度下，淋巴细胞增殖未受影响。给携带L1210白血病的小鼠体内注射ADMU（40毫克/千克，在第1至3天每天两次），仅在接种白血病后的第6天导致肿瘤细胞数量短暂且持续时间短的减少。