甲基胆蒽诱导酶活性的机制研究

Harry V. Gelboin
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引用次数: 54

摘要

体内给药3-甲基胆蒽(MC)增加体外大鼠肝脏微粒体和核糖体氨基酸掺入。mc处理大鼠的微粒体氨基酸合并系统与正常制剂具有相同的辅助因子需求。在相同浓度的MgCl2、GSH和GTP时,两种制剂均表现出最佳的掺入效果,并且两种制剂对嘌呤霉素的抑制同样敏感。mc诱导的氨基酸掺入增加至少部分是由于活跃微粒体掺入位点数量的增加和微粒体信使rna含量的明显增加。在预孵育过程中,信使RNA的损失率在正常和MC微粒体中是相同的。通过预孵育去除信使RNA后,l-[14C]苯丙氨酸的掺入完全依赖于添加的多尿苷酸。在多尿苷酸饱和的情况下,预孵育的MC微粒体比预孵育的正常微粒体含有更多的l-[14C]苯丙氨酸。MC对氨基酸掺入的影响与MC诱导的肝苯并芘羟化酶活性的增加是平行的。放线菌素- d可阻止MC对微粒体氨基酸掺入和酶活性的刺激作用。讨论了MC对酶形成系统的影响与癌变之间的可能关系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Studies on the mechanism of methylcholanthrene induction of enzyme activities

The administration in vivo of 3-methylcholanthrene (MC) increases microsomal and ribosomal amino acid incorporation in vitro in rat liver. The microsomal amino acid incorporating system from MC-treated rats has the same cofactor requirements as does the normal preparation. Both preparations exhibit optimal incorporation at the same concentration of MgCl2, GSH, and GTP and both preparations are equally sensitive to puromycin inhibition. The MC-induced increase in amino acid incorporation is due at least in part to an increase in the number of active microsomal incorporation sites and an apparent increase in the messenger-RNA content of the microsomes. The rate of loss of messenger RNA during a preincubation is the same in normal and MC microsomes. After removal of messenger RNA by preincubation, l-[14C]phenylalanine incorporation is completely dependent on added polyuridylic acid. In the presence of saturating levels of polyuridylic acid, the preincubated MC microsomes incorporate greater amounts of l-[14C]phenylalanine than do preincubated normal microsomes.

The MC effect on amino acid incorporation is paralleled by an MC-induced increase in the activity of liver benzpyrene hydroxylase. Administration of actinomycin-D prevents the stimulatory effect of MC on microsomal amino acid incorporation and on enzyme activity. The possible relationship between the effects of MC on the enzyme forming system and carcinogenesis are discussed.

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