Mechanistic relationships between hepatic genotoxicity and carcinogenicity in male B6C3F1 mice treated with polycyclic aromatic hydrocarbon mixtures.
Mechanistic relationships between hepatic genotoxicity and carcinogenicity in male B6C3F1 mice treated with polycyclic aromatic hydrocarbon mixtures.
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DOI：
10.1007/s00204-014-1285-8
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发表时间：
2015-06
影响因子：
6.1
通讯作者：
Zhou, Guo-Dong
中科院分区：
文献类型：
--
作者：
Phillips, Tracie D.;Richardson, Molly;Cheng, Yi-Shing Lisa;He, Lingyu;McDonald, Thomas J.;Cizmas, Leslie H.;Safe, Stephen H.;Donnelly, Kirby C.;Wang, Fen;Moorthy, Bhagavatula;Zhou, Guo-Dong
关键词：
通过测定暴露于3种不同剂量的化学混合物的雄性B6 C3 F1小鼠的DNA加合物和肿瘤发生率，研究了木材防腐废物和重组混合物（RM）的复杂混合物[中性组分（NF）]的遗传毒性，该混合物模拟了含有7种主要多环芳烃（PAH）和苯并（a）芘（BaP）的NF。DNA加合物在24 h后出现峰值，NF+BaP组小鼠PAH-DNA加合物水平最高，肿瘤发生率和死亡率也最高。1，7，或21天后的DNA加合物水平显着相关的动物死亡率和总肿瘤，包括肝，肺和前胃的发病率。然而，只有肝脏DNA加合物后7天显着相关的肝肿瘤的发病率。与非肿瘤组织相比，大多数参与DNA修复的蛋白质包括ATM、pATR、Chk 1、pChk 1、DNA PKcs、XRCC 1、FANCD 2、Ku 80、Mre 11和Brca 2在肝肿瘤组织中显著降低。参与细胞凋亡和细胞周期调控的蛋白质的表达在肿瘤与非肿瘤组织中也有显着差异，可能PAH诱导的这些基因产物的变化对肿瘤的发展和生长很重要。
The genotoxicity of a complex mixture [neutral fraction (NF)] from a wood preserving waste and reconstituted mixture (RM) mimicking the NF with seven major polycyclic aromatic hydrocarbons (PAHs) and benzo(a)pyrene (BaP) was investigated by determining DNA adducts and tumor incidence in male B6C3F1 mice exposed to 3 different doses of the chemical mixtures. The peak values of DNA adducts were observed after 24 h and the highest levels of PAH-DNA adducts were exhibited in mice administered NF+BaP, and the highest tumor incidence and mortality were also observed in this group. DNA adduct levels after 1, 7, or 21 d were significantly correlated with animal mortality and incidence of total tumors including liver, lung, and forestomach. However, only hepatic DNA adducts after 7 d significantly correlated with liver tumor incidence. Most proteins involved in DNA repair including ATM, pATR, Chk1, pChk1, DNA PKcs, XRCC1, FANCD2, Ku80, Mre11 and Brca2 were significantly lower in liver tumor tissue compared to non-tumor tissue. Expression of proteins involved in apoptosis and cell cycle regulation were also significantly different in tumor vs non-tumor tissues and it is possible that PAH-induced changes in these gene products are important for tumor development and growth.
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影响因子：
2.9
作者：
Hu, WW;Feng, ZH;Tang, MS
通讯作者：
Tang, MS
DOI：
10.1016/j.mrrev.2008.03.006
发表时间：
2008-07-01
影响因子：
5.3
作者：
Farmer, Peter B.;Singh, Rajinder
通讯作者：
Singh, Rajinder
DOI：
10.1073/pnas.81.22.6943
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
GUPTA, RC
通讯作者：
GUPTA, RC
影响因子：
5.1
作者：
Randerath, K;Sriram, P;Watson, WP
通讯作者：
Watson, WP
影响因子：
64.8
作者：
JEFFREY, AM;WEINSTEIN, IB;HARRIS, C
通讯作者：
HARRIS, C