NC State Gene ‘Knockout’ Floors Tobacco Carcinogen

在大规模的田间试验中，来自北卡罗来纳州立大学的科学家表明，沉默烟草植物中的特定基因显着减少了固化烟草叶中的有害致癌物质。

The finding could lead to tobacco products – especially smokeless products – with reduced amounts of cancer-causing agents.

NC State’s Dr. Ralph Dewey, professor of crop science, and Dr. Ramsey Lewis, assistant professor of crop science, teamed with colleagues from the University of Kentucky to knock out a gene known to turn nicotine into nornicotine. Nornicotine is a precursor to the carcinogen N-nitrosonornicotine (NNN). Varying percentages of nicotine are turned into nornicotine while the plant ages; nornicotine converts to NNN as the tobacco is cured, processed and stored.

The field tests in Kentucky, Virginia and North Carolina compared cured burley tobacco plants with the troublesome gene silenced and “control” plant lines with normal levels of gene expression. The researchers found a six-fold decrease in carcinogenic NNN in the genetically modified tobacco plants, as well as a 50 percent overall reduction in the class of harmful compounds called TSNAs, or tobacco-specific nitrosamines. TSNAs are reported to be among the most important tobacco-related compounds implicated in various cancers in laboratory experiments, Lewis said.

The research results were published online inPlant Biotechnology Journal.

Lewis and Dewey stress that the best way for people to avoid the risks associated with tobacco use is to avoid using tobacco products. But their findings show that targeted gene silencing can work as well in the field as it does on the lab bench.

“杜威说：”用较少或没有有害化合物制造烟草植物也可能​​有助于制造药品或其他高价值产品的烟草植物。“

To get initial lines of plants with the troublesome gene silenced, the NC State researchers used a technique called RNA interference in which genetic engineering was used to introduce a gene that inhibits the demethylase gene function into the tobacco plant.

杜威和刘易斯已经开发出烟草线，而不使用基因工程的效果。将它们随机插入化学改变或突变，进入伯利烟草植物的烟草基因组。然后，它们搜索植物，其中尼古丁去甲基化酶基因被永久损害。研究人员目前正在努力将这种突变转移到广泛使用的烟草品种。

Dewey and Lewis add that nothing else in the plant changed – growth or resistance to insects or disease, for example – after they knocked out this specific gene.

虽然刘易斯认为，在未来几年内，刘易斯在未来几年内将存在沉默的去甲基化酶基因的品种，但NC国家研究人员表示，Burley烟草具有许多其他靶向其基因沉默方法。

The research is sponsored by Philip Morris USA.

- kulikowski

Note to editors: An abstract of the paper follows.

“RNA干扰（RNAi） - 抑制尼古丁去甲基酶活性的抑制减少了固化的烟草叶片中的关键致癌水平”
作者：Ramsey S. Lewis和北卡罗来纳州州立大学的Ralph E. Dewey;Anne M. Jack，Lily Gavilano，Balazs Siminszky和洛杉矶大学洛杉矶州;杰里莫里斯，文森·罗伯特和阿里克海耶斯，菲利普莫里斯美国
发布：2月14日在线Plant Biotechnology Journal

Abstract: Technologies for reducing the levels of tobacco product constituents that may contribute to unwanted health effects are desired. Target compounds include tobacco-specific nitrosamines (TSNAs), a class of compounds generated through the nitrosation of pyridine alkaloids during the curing and processing of tobacco. Studies have reported the TSNA N’-nitrosonornicotine (NNN) to be carcinogenic in laboratory animals. NNN is formed via the nitrosation of nornicotine, a secondary alkaloid produced through enzymatic N-demethylation of nicotine. Strategies to lower nornicotine levels in tobacco (Nicotiana tabacum L.) could lead to a corresponding decrease in NNN accumulation in cured leaves. The major nicotine demethylase gene of tobacco has recently been isolated. In this study, a large-scale field trial was conducted to evaluate transgenic lines of burley tobacco carrying an RNA interference (RNAi) construct designed to inhibit the expression of this gene. Selected transgenic lines exhibited a six-fold decrease in nornicotine content relative to untransformed controls. Analysis of cured leaves revealed a commensurate decrease in NNN and total TSNAs. The inhibition of nicotine demethylase activity is an effective means of decreasing significantly the level of a key defined animal carcinogen present in tobacco products.