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对燃烧或主要加热烟草的香烟烟雾冷凝物经皮肤涂抹后在小鼠体内形成DNA加合物的比较研究。

Comparative studies of DNA adduct formation in mice following dermal application of smoke condensates from cigarettes that burn or primarily heat tobacco.

作者信息

Brown B, Kolesar J, Lindberg K, Meckley D, Mosberg A, Doolittle D

机构信息

Product Evaluation, Research and Development, R.J. Reynolds Tobacco, Winston-Salem, NC 27102, USA.

出版信息

Mutat Res. 1998 May 11;414(1-3):21-30. doi: 10.1016/s1383-5718(98)00035-7.

Abstract

A new cigarette (Eclipse) that primarily heats rather than burns tobacco has been developed. Since Eclipse primarily heats tobacco, the smoke chemistry is much simplified, consisting of 80% glycerol and water. With the simplified smoke chemistry, it would be expected that toxicological activity would be reduced. Smoke and smoke condensate from Eclipse have consistently yielded markedly reduced mutagenicity and cytotoxicity in in vitro tests when compared to smoke and smoke condensate from the 1R4F Kentucky reference cigarette, which is representative of typical low 'tar' cigarettes sold in the U.S. today. The objective of the present study was to evaluate the potential of mainstream cigarette smoke condensate (CSC) of Eclipse to produce DNA adducts in lung, heart and skin tissue of dermally-exposed mice and to compare the results with those obtained with CSC from the 1R4F Kentucky reference cigarette. CSC from Eclipse or 1R4F cigarettes was applied dermally to SENCAR mice three times a week for 30 weeks. Amounts of CSC applied were 30, 60 or 120 mg 'tar' per animal per week. Tissues were collected after 1, 4, 14 and 29 weeks of CSC application. DNA adducts were analyzed in lung, heart and skin tissues using the 32P-postlabeling method with P1 nuclease modification. Distinct time and dose-dependent diagonal radioactive zones (DRZ) were observed in the DNA from lung, heart and skin tissues of animals treated with 1R4F CSC. The relative adduct labeling (RAL) values of lung, heart and skin DNA from reference CSC-treated animals were significantly greater (p<0.05) than those of the solvent control animals. No corresponding DRZs were observed at any dose from the DNA of animals treated with CSC from Eclipse or solvent control (acetone) and the RAL values observed following application of Eclipse were not increased relative to the solvent control. These results provide additional evidence that the smoke condensate from the Eclipse cigarette is markedly less genotoxic than smoke condensate from tobacco-burning cigarettes representative of those currently sold in the U.S.

摘要

一种主要加热而非燃烧烟草的新型香烟(日蚀牌)已研制出来。由于日蚀牌香烟主要是加热烟草,其烟雾化学成分大大简化,由80%的甘油和水组成。随着烟雾化学成分的简化,可以预期其毒理学活性会降低。与代表当今美国销售的典型低“焦油”香烟的1R4F肯塔基参考香烟的烟雾和烟雾冷凝物相比,日蚀牌香烟的烟雾和烟雾冷凝物在体外试验中始终产生明显降低的致突变性和细胞毒性。本研究的目的是评估日蚀牌香烟主流烟雾冷凝物(CSC)在经皮肤暴露的小鼠的肺、心脏和皮肤组织中产生DNA加合物的潜力,并将结果与用1R4F肯塔基参考香烟的CSC获得的结果进行比较。将日蚀牌或1R4F香烟的CSC每周三次经皮肤应用于SENCAR小鼠,持续30周。每只动物每周应用的CSC量为30、60或120毫克“焦油”。在应用CSC 1、4、14和29周后收集组织。使用经P1核酸酶修饰的³²P后标记法分析肺、心脏和皮肤组织中的DNA加合物。在用1R4F CSC处理的动物的肺、心脏和皮肤组织的DNA中观察到明显的时间和剂量依赖性对角放射性区(DRZ)。来自参考CSC处理动物的肺、心脏和皮肤DNA的相对加合物标记(RAL)值显著高于(p<0.05)溶剂对照动物。在用日蚀牌香烟的CSC处理的动物的DNA中,在任何剂量下均未观察到相应的DRZ,并且应用日蚀牌香烟后观察到的RAL值相对于溶剂对照没有增加。这些结果提供了额外的证据,即日蚀牌香烟的烟雾冷凝物的遗传毒性明显低于代表目前在美国销售的燃烧烟草香烟的烟雾冷凝物。

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