Brown D M, Horsman M R, Hirst D G, Brown J M
Int J Radiat Oncol Biol Phys. 1984 Sep;10(9):1665-8. doi: 10.1016/0360-3016(84)90524-8.
In these preliminary experiments, we have found enhanced cell killing by the bifunctional alkylating agent L-phenylalanine mustard (L-PAM) in the presence of inhibitors of poly (ADP-ribose) polymerase (ADPRP) in vitro. In vivo enhancement of the tumoricidal effects of L-PAM was observed with the ADPRP inhibitor nicotinamide (1000 mg/kg), although enhanced myelosuppression was also demonstrated. Nicotinamide also increased the plasma elimination half-life of L-PAM by a factor of at least 2. This alteration of L-PAm pharmacokinetics makes it difficult to assess the role that ADPRP inhibition plays in the enhancement of L-PAM tumor cell killing in vivo.
在这些初步实验中，我们发现，在体外，双功能烷化剂L-苯丙氨酸氮芥（L-PAM）在聚（ADP-核糖）聚合酶（ADPRP）抑制剂存在的情况下，细胞杀伤作用增强。使用ADPRP抑制剂烟酰胺（1000毫克/千克）时，观察到L-PAM的体内杀肿瘤作用增强，尽管也证实有骨髓抑制增强的情况。烟酰胺还使L-PAM的血浆消除半衰期延长至少2倍。L-PAM药代动力学的这种改变使得难以评估ADPRP抑制在体内增强L-PAM对肿瘤细胞杀伤作用中所起的作用。
