N-2-乙酰氨基芴对暴露于表皮生长因子的培养大鼠肝细胞中多聚（ADP-核糖）聚合酶活性和DNA合成的影响。

Effect of N-2-acetylaminofluorene on poly(ADP-ribose) polymerase activity and DNA synthesis in cultured rat hepatocytes exposed to epidermal growth factor.

作者信息

Scarabelli L, Cesarone C F, Giannoni P, Porotto A, Gallo G, Orunesu M

机构信息

Istituto di Fisiologia Generale, Universitá di Genova.

出版信息

Boll Soc Ital Biol Sper. 1992 Jan;68(1):55-62.

PMID:1503739

Abstract

The nuclear enzyme poly(ADP-ribose) polymerase is involved in basic cellular processes such as DNA replication and repair, cell differentiation and transformation, gene expression. We have studied the effect of 2AAF, a genotoxic aromatic amine, on pADPRP activity during DNA synthesis stimulated by EGF, using the cultured rat hepatocytes model. DNA synthesis was measured as [3H]thymidine incorporated/microgram DNA while pADPRP activity was expressed in pmol[32P]NAD incorporated/min/microgram DNA. Our results show that 2AAF treatment of EGF-stimulated rat hepatocytes induces a full block of DNA replication which is preceded and accompanied by a net inhibition of endogenous and total pADPRP activity, respectively. A block in pADPRP activity in normal hepatocytes, exposed to 2AAF in vitro or in vivo, could play a key role in cell transformation. Our data add further information on the possible involvement of this nuclear catalytic activity during DNA replication.

摘要

核酶聚（ADP - 核糖）聚合酶参与DNA复制与修复、细胞分化与转化、基因表达等基本细胞过程。我们使用培养的大鼠肝细胞模型，研究了遗传毒性芳香胺2 - 乙酰氨基芴（2AAF）对表皮生长因子（EGF）刺激的DNA合成过程中聚（ADP - 核糖）聚合酶（pADPRP）活性的影响。DNA合成以掺入的[³H]胸苷/微克DNA来衡量，而pADPRP活性则以掺入的pmol[³²P]NAD/分钟/微克DNA来表示。我们的结果表明，用2AAF处理EGF刺激的大鼠肝细胞会导致DNA复制完全受阻，在此之前和同时分别伴随着内源性和总pADPRP活性的净抑制。在体外或体内暴露于2AAF的正常肝细胞中，pADPRP活性的阻断可能在细胞转化中起关键作用。我们的数据进一步提供了关于这种核催化活性在DNA复制过程中可能参与情况的信息。