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In ovo testing of flavor and fragrance materials in Turkey Egg Genotoxicity Assay (TEGA), comparison of results to in vitro and in vivo data
Food and Chemical Toxicology ( IF 4.3 ) Pub Date : 2018-03-13 , DOI: 10.1016/j.fct.2018.03.015
Tetyana Kobets , Jian-Dong Duan , Klaus D. Brunnemann , Michael J. Iatropoulos , Sylvain Etter , Christina Hickey , Benjamin Smith , Gary M. Williams

Genotoxicity of flavor and fragrance materials was assessed in Turkey Egg Genotoxicity Assay (TEGA) using 32P-nucleotide postlabeling (NPL) and comet assays to detect hepatic DNA adducts and strand breaks. Twenty materials having results in GADD45a-Gluc ‘BlueScreen HC’ genotoxicity assay, and standard in vitro and in vivo tests, were selected to evaluate the accuracy of TEGA. Quinoline (QUI) and 2-acetylaminofluorene (AAF) served as positive comparators.

Two materials, p-tert-butyldihydrocinnamaldehyde (BDHCA) and methyl eugenol (MEU) produced DNA adducts. BDHCA, p-t-butyl-α-methylhydrocinnamic aldehyde (BMHCA), trans-2-hexenal (HEX) and maltol (MAL) produced DNA strand breaks. Fifteen other materials were negative in both assays. Based on reports of oxidative DNA damage induction by MAL and 4-hydroxy-2.5-dimethyl-3(2H) furanone (HDMF), modified comet assays were conducted. Positive comet findings for MAL were not confirmed, and only equivocal evidence of oxidative damage was found. Accordingly, MAL was judged to have equivocal genotoxicity in TEGA. HDMF was positive in modified comet assay, indicating an ability to produce oxidative DNA damage.

TEGA showed modest concordance with results in regulatory in vitro assays. Findings in TEGA, with few exceptions, were concordant with the results of in vivo genotoxicity and carcinogenicity testing. Thus, TEGA is an attractive alternative model for the assessment of genotoxic potential of chemicals in vivo.



中文翻译:

土耳其鸡蛋遗传毒性测定(TEGA)中对香精和香精材料的卵内测试中,将结果与体外体内数据进行比较

使用32 P核苷酸后标记(NPL)和彗星分析法检测土耳其DNA加合物和链断裂,在土耳其鸡蛋遗传毒性分析法(TEGA)中评估了香精和香料材料的遗传毒性。选择二十种在GADD45a-Gluc'BlueScreen HC'遗传毒性试验中获得结果的材料,以及标准的体外体内试验,以评估TEGA的准确性。喹啉(QUI)和2-乙酰氨基芴(AAF)作为阳性对照。

对-叔丁基二氢肉桂醛(BDHCA)和甲基丁子香酚(MEU)这两种材料产生了DNA加合物。BDHCA,对-丁基-α-甲基氢肉桂醛(BMHCA),反式-2-己醛(HEX)和麦芽酚(MAL)产生了DNA链断裂。在这两种测定中,其他15种物质均为阴性。根据MAL和4-羟基-2.5-二甲基-3(2H)呋喃酮(HDMF)诱导的DNA氧化损伤的报道,进行了改进的彗星试验。未确认到MAL的阳性彗星发现,仅发现了氧化损伤的模棱两可的证据。因此,MAL被认为在TEGA中具有模棱两可的遗传毒性。HDMF在改良彗星试验中呈阳性,表明具有产生氧化DNA损伤的能力。

TEGA与体外监管试验的结果显示出适度的一致性。除少数例外,TEGA中的发现与体内遗传毒性和致癌性测试的结果一致。因此,TEGA是用于评估体内化学物质潜在遗传毒性的有吸引力的替代模型。

更新日期:2018-03-13
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