Increased nucleoside triphosphatase activity of rat liver nuclear envelope is associated with hepatocarcinogen exposure

Gary Clawson, D. E. Moody, L. D. Ferrell, E. A. Smuckler

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Altered transport of nuclear RNA sequences is an early response to carcinogens. Nuclear envelopes (NE) were isolated and assayed for nucleoside triphosphatase activity (NTPase), on the premise that this enzymatic activity participates in RNA transport. A common feature of the action of five different carcinogens (thioacetamide, 2-acetylaminofluorene, 3'-methyl-4-dimethylaminoazobenzene, dimethylnitrosamine, and aflatoxin B1), at low doses without significant toxicity, was to increase NE NTPase activity and to increase RNA transport, as assessed by the appearance of rapidly labeled RNA in the cytoplasm and by in vitro assay. The increases in the NTPase were specific for the NE fraction, and early toxic effects of higher doses initially masked the increases. The induced increases in the NE NTPase were long-lived. In contrast, increases in NE NTPase were observed only during the regenerative phase of CCL4 intoxication, the CCl4-induced increase was short-lived and returned promptly to control levels. These changes in NTPase activity were not associated with parallel changes in phosphorylation/dephosphorylation of NE proteins. Increases in NE NTPase and alterations in RNA transport, without attendant nuclear replication, may relate to altered nuclear RNA restriction. This change in a regulatory phenomenon may make these cells more susceptible to further modification, potentially playing a role in the initiation phase of carcinogenesis

Original languageEnglish (US)
Pages (from-to)682-689
Number of pages8
JournalLaboratory Investigation
Volume51
Issue number6
StatePublished - 1984

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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