化学诱发大鼠肝癌的亚细胞组分中两类丝氨酸蛋白激酶的动态变化

用二乙基亚硝胺（ＤＥＮ）诱发大鼠肝癌，隔周测定肝脏胞液、膜性和胞核中的蛋白激酶Ａ（ＰＫＡ）和蛋白激酶Ｃ（ＰＫＣ）的活力。发现胞液ＰＫＡ在诱癌过程中活力改变不大，胞液ＰＫＣ则逐步增高，在第１３周和２０周形成两个活力高峰。膜性ＰＫＡ和ＰＫＣ都呈双相变化，即在癌前期（１０－１４周）增加，癌形成期（１７－２０周）反而降至正常以下，胞核ＰＫＡ和ＰＫＣ也都在癌前期升至高峰，而癌形成期则低于癌前期，但仍高于正常（ＰＫＡ）或接近正常（ＰＫＣ）。因只有膜性ＰＫＣ在大鼠老化时降低，故这些变化不是鼠龄变化的结果，而是ＤＥＮ诱癌所引起，其变化机理可能与下降调节、细胞内转位或两型同工酶相反的升降变化有关。

Dynamic Changes of Two Serine Protein Kinases in Subcellular Fraction during the Development of Chemical Induced Hepatocarcinoma

Rat hepatocarcinoma was induced by N-nitrosediethylamine(DEN), and the activities of protein kinase A (PKA)and protein kinase C(PKC) in liver cytosolic, membranous and nuclear fraction were determined every two weeks. It was found that the cytosolic PKA was not changed during the development of carcinogenesis, but cytosolic PKC was gradually increased, exhibiting two peaks at 13th and 20th week from the beginning of DEN treatment. Both membranous PKA and PKC showed a biphasic profile, being increased at the precancerous stage(10th-14th), and decreased to lower than normal (o week) level at the cancerous stage. Nuclear PKA and PKC were also elavated to maximum at precancerous stage, and declined at cancerous stage,but still higher (PKA)than or closed to normal control value (PKC).These changes were the results of the carcinogenic effect of DEN rather than the effect of rat aging, because only liver membranous PKC was decreased in old rats. The mechanism of the activity changes may be due to the down regulation, intracellular translocation or the opposite changes of two isozymes of PKA or PKC.