Zittoun J, Marquet J, Pilorget J J, Tonetti C, De Gialluly E
Service Central d'Hématologie-Immunologie, Hôpital Henri Mondor Faculté de Médecine, Creteil, France.
Br J Cancer. 1991 Jun;63(6):885-8. doi: 10.1038/bjc.1991.194.
The comparative efficacy of the pure diastereoisomers of leucovorin, the natural (6S) and the unnatural (6R) forms was compared to the racemic form (6RS). A protective effect in methotrexate-treated CCRF-CEM cells was obtained with 6S at concentrations 100-fold higher than those of methotrexate and with 6RS at concentrations 2-fold greater than those of 6S; however, at low concentrations of methotrexate, 6S was more effective than 6RS in preventing the cytotoxicity of methotrexate; on the opposite, 6R exhibited a protective effect at concentrations 10(4) higher than those of methotrexate. On the same cell line, 6S was shown to enhance the cytotoxic effect of 5 Fluorouracil exactly as 6RS while 6R did not exhibit any enhancing effect on cells exposed to 5 Fluorouracil.
对亚叶酸的纯非对映异构体(天然的(6S)形式和非天然的(6R)形式)与消旋形式(6RS)的比较疗效进行了研究。在甲氨蝶呤处理的CCRF - CEM细胞中,(6S)在浓度比甲氨蝶呤高100倍时具有保护作用,(6RS)在浓度比(6S)高2倍时具有保护作用;然而,在低浓度甲氨蝶呤时,(6S)在预防甲氨蝶呤细胞毒性方面比(6RS)更有效;相反,(6R)在浓度比甲氨蝶呤高10⁴倍时表现出保护作用。在同一细胞系中,(6S)被证明与(6RS)一样能增强5-氟尿嘧啶的细胞毒性作用,而(6R)对暴露于5-氟尿嘧啶的细胞没有任何增强作用。