Taylor I W, Slowiaczek P, Francis P R, Tattersall M H
Cancer Res. 1982 Dec;42(12):5159-64.
The modulation of MTX cytotoxicity by purines has been studied in a number of mammalian cell lines. In each case, it was found that exogenous purines (guanosine, deoxyguanosine, adenosine, deoxyadenosine, and hypoxanthine) both reduced and potentiated MTX cytotoxicity depending on the MTX concentration. At low MTX concentrations (less than 6 X 10(-8) M), purines reduced MTX toxicity and at higher concentrations they potentiated MTX toxicity. The reduction of low-concentration MTX cytotoxicity by purines was associated with the reversal of MTX-induced changes in deoxyribonucleotide pools. On the other hand, potentiation of MTX toxicity by purines was associated with substantial increases in deoxyadenosine 5'-triphosphate levels in conjunction with low deoxythymidine 5'-triphosphate levels. The magnitude of increase in deoxyadenosine 5'-triphosphate levels tended to correlate with the degree of potentiation which varied between 5-fold and 200-fold, depending on cell type and the exogenous purine.
嘌呤对甲氨蝶呤（MTX）细胞毒性的调节作用已在多种哺乳动物细胞系中进行了研究。在每种情况下，都发现外源性嘌呤（鸟苷、脱氧鸟苷、腺苷、脱氧腺苷和次黄嘌呤）根据MTX浓度既降低又增强了MTX的细胞毒性。在低MTX浓度（低于6×10⁻⁸ M）时，嘌呤降低MTX毒性，而在较高浓度时则增强MTX毒性。嘌呤对低浓度MTX细胞毒性的降低与MTX诱导的脱氧核苷酸池变化的逆转有关。另一方面，嘌呤对MTX毒性的增强与脱氧腺苷5'-三磷酸水平的大幅增加以及低脱氧胸苷5'-三磷酸水平有关。脱氧腺苷5'-三磷酸水平的增加幅度往往与增强程度相关，增强程度在5倍至200倍之间变化，这取决于细胞类型和外源性嘌呤。
