Slocum H K, Hakala M T
Cancer Res. 1975 Feb;35(2):423-8.
Twenty-one cell lines (six human lines, and nine mouse lines) were compared with respect to inhibition of growth by N-6-(delta-2-isopentenyl)adenosine (IPAR). Six of these, mouse Sarcoma 180, Ehrilich ascites carcinoma, mammary adenocarconoma (TA3), leukemia L1210, mouse kidney, and canine kidney cells, differed by up to 16-fold with respect to their sensitivity and were chosen for further study. One factor contributing to the resistance was a slower formation of intracellular 5-monophosphate of IPAR (IPAMP) due to reduced adenosine kinase activity. Because of this slower formation of IPAMP in the resistant cells, a higher extracellular IPAR was required for the maintenance of equal intracellular IPAMP levels. Regardless of the degree of resistance, the rate of decay of intracellular IPAMP was similar and very rapid, with a half-life of 37 plus or minus 5 min. In the sensitive cells IPAMP was cleaved back to IPAR, while in the resistant cells IPAR was cleaved further to the free base, N-6-(delta-2-isopentenyl)adenine (IPA), which accumulated in the medium. The rate of formation of IPA constitutes an irreversible inactivation of IPAR, because IPA is not converted back to IPAMP and is not growth inhibitory. In one of the resistant cells (mouse kidney) the inactivation was so rapid that in 1 hr 25% of the extracellular (30 muM) IPAR was converted to IPA.
对21种细胞系（6种人类细胞系和9种小鼠细胞系）进行了N⁶-(δ²-异戊烯基)腺苷（IPAR）对生长抑制作用的比较。其中6种，即小鼠肉瘤180、艾氏腹水癌、乳腺腺癌（TA3）、白血病L1210、小鼠肾细胞和犬肾细胞，其敏感性差异高达16倍，并被选作进一步研究。导致耐药的一个因素是由于腺苷激酶活性降低，细胞内IPAR的5-单磷酸（IPAMP）形成较慢。由于耐药细胞中IPAMP形成较慢，因此需要更高的细胞外IPAR来维持相等的细胞内IPAMP水平。无论耐药程度如何，细胞内IPAMP的衰减速率相似且非常快，半衰期为37±5分钟。在敏感细胞中，IPAMP被裂解回IPAR，而在耐药细胞中，IPAR进一步裂解为游离碱N⁶-(δ²-异戊烯基)腺嘌呤（IPA），后者在培养基中积累。IPA的形成速率构成了IPAR的不可逆失活，因为IPA不会再转化回IPAMP，且没有生长抑制作用。在其中一种耐药细胞（小鼠肾细胞）中，失活非常迅速，以至于在1小时内，25%的细胞外（30μM）IPAR被转化为IPA。
