In vitro and in silico genetic toxicity screening of flavor compounds and other ingredients in tobacco products with emphasis on ENDS

遗传毒性 碎屑成因 生物信息学 数量结构-活动关系 计算生物学 微核试验 DNA损伤 优先次序 致癌物 毒理 化学 生物 遗传学 药理学 毒性 DNA 生物信息学 基因 经济 有机化学 管理科学
作者
Pei‐Hsuan Hung,Matthew Savidge,Mamata De,Juei-Chuan C. Kang-Sickel,Sheila M. Healy,Luis G. Valerio
出处
期刊:Journal of Applied Toxicology [Wiley]
卷期号:40 (11): 1566-1587 被引量:7
标识
DOI:10.1002/jat.4020
摘要

Electronic nicotine delivery systems (ENDS) are regulated tobacco products and often contain flavor compounds. Given the concern of increased use and the appeal of ENDS by young people, evaluating the potential of flavors to induce DNA damage is important for health hazard identification. In this study, alternative methods were used as prioritization tools to study the genotoxic mode of action (MoA) of 150 flavor compounds. In particular, clastogen-sensitive (γH2AX and p53) and aneugen-sensitive (p-H3 and polyploidy) biomarkers of DNA damage in human TK6 cells were aggregated through a supervised three-pronged ensemble machine learning prediction model to prioritize chemicals based on genotoxicity. In addition, in silico quantitative structure-activity relationship (QSAR) models were used to predict genotoxicity and carcinogenic potential. The in vitro assay identified 25 flavors as positive for genotoxicity: 15 clastogenic, eight aneugenic and two with a mixed MoA (clastogenic and aneugenic). Twenty-three of these 25 flavors predicted to induce DNA damage in vitro are documented in public literature to be in e-liquid or in the aerosols produced by ENDS products with youth-appealing flavors and names. QSAR models predicted 46 (31%) of 150 compounds having at least one positive call for mutagenicity, clastogenicity or rodent carcinogenicity, 49 (33%) compounds were predicted negative for all three endpoints, and remaining compounds had no prediction call. The parallel use of these predictive technologies to elucidate MoAs for potential genetic damage, hold utility as a screening strategy. This study is the first high-content and high-throughput genotoxicity screening study with an emphasis on flavors in ENDS products.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
完美世界应助风清扬采纳,获得10
刚刚
英姑应助lllllllll采纳,获得10
刚刚
Orange应助殷勤的白玉采纳,获得10
刚刚
大威天龙完成签到,获得积分10
1秒前
乐乐应助可耐的发夹采纳,获得10
1秒前
烟花应助lili采纳,获得10
1秒前
1秒前
骆風发布了新的文献求助10
2秒前
2秒前
归尘发布了新的文献求助10
3秒前
Nnn发布了新的文献求助100
3秒前
catalysisman完成签到,获得积分10
3秒前
十八完成签到,获得积分10
3秒前
fvsuar完成签到,获得积分10
4秒前
4秒前
初一完成签到,获得积分10
4秒前
fj发布了新的文献求助10
5秒前
香蕉觅云应助沉默的尔槐采纳,获得10
5秒前
JamesPei应助骆風采纳,获得10
5秒前
andrewyu发布了新的文献求助10
5秒前
喜悦的丹妗完成签到,获得积分20
6秒前
阿冰发布了新的文献求助10
6秒前
7秒前
大方板栗完成签到,获得积分10
7秒前
科研圣体发布了新的文献求助10
7秒前
7秒前
聪慧芷巧发布了新的文献求助10
8秒前
方不慌完成签到,获得积分10
8秒前
宋子琛发布了新的文献求助10
9秒前
畅快的觅风完成签到,获得积分20
9秒前
852应助吃点红糖馒头采纳,获得10
9秒前
9秒前
10秒前
江江江完成签到,获得积分20
11秒前
煎饼煎饼发布了新的文献求助10
11秒前
脑洞疼应助风清扬采纳,获得10
12秒前
12秒前
Cartman完成签到,获得积分10
12秒前
共享精神应助vicky采纳,获得10
13秒前
高分求助中
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
Effective Learning and Mental Wellbeing 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3974779
求助须知:如何正确求助?哪些是违规求助? 3519193
关于积分的说明 11197417
捐赠科研通 3255311
什么是DOI,文献DOI怎么找? 1797760
邀请新用户注册赠送积分活动 877150
科研通“疑难数据库(出版商)”最低求助积分说明 806187