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在小鼠淋巴瘤试验中对蒽醌染料的遗传毒性分析。

Analysis of the genotoxicity of anthraquinone dyes in the mouse lymphoma assay.

作者信息

Harrington-Brock K, Parker L, Doerr C, Cimino M C, Moore M M

机构信息

Environmental Health Research and Testing, Inc., Research Triangle Park, NC 27709.

出版信息

Mutagenesis. 1991 Jan;6(1):35-46. doi: 10.1093/mutage/6.1.35.

DOI:10.1093/mutage/6.1.35
PMID:2038271
Abstract

Despite their widespread use and potential for significant human exposure, genotoxicity data on anthraquinones and other dyes are limited. In this study, 16 anthraquinones and one azo dye (Solvent Red 1) were selected for testing using the thymidine kinase (tk) locus and micronucleus (MN) analysis in L5178Y/TK(+/-)-3.7.2C mouse lymphoma cells. Six of the dyes were from the same lot used in the NTP rodent bioassay. The dyes used were all production lots and thus varied in their purity. Disperse Blue 7, 2-aminoanthraquinone, 1-amino-2-methylanthraquinone, Disperse Blue 3 and Disperse Red 11 were genotoxic (inducing 1814 mutants/10(6) survivors, 369 MN/1000 cells at 13% survival; 397 mutants/10(6) survivors, 196 MN/1000 cells at 21% survival; 178 mutants/10(6) survivors, 119 MN/1000 cells at 51% survival; 264 mutants/10(6) survivors, 109 MN/1000 cells at 15% survival, respectively). Reactive Blue 19 was weakly mutagenic (inducing 144 mutants/10(6) survivors, but only 8 MN/1000 cells at 13% survival). Vat Yellow 4 and Solvent Red 1, with exogenous activation, were also mutagenic (inducing 300 mutants/10(6) survivors, 18 MN/1000 cells at 57% survival, and 100 mutants/10(6) survivors and 16 MN/1000 cells at 22% survival, respectively). With activation 1-nitro-2-methylanthraquinone was judged to give an equivocal mutagenicity response. The maximum test concentration was limited for some compounds by their solubility. Those chemicals that did not induce mutation or cytotoxicity at the limits of solubility were classified separately. Compounds which were not evaluated without exogenous activation because of insolubility but were evaluated with activation include 1-nitro-2-methylanthraquinone, Solvent Red 1 and Vat Yellow 4. Compounds which were not evaluated either with or without S9 activation because of their insolubility in the culture medium include 1-amino-2,4-dibromoanthraquinone, D&C Green, Disperse Blue 1, Disperse Red 60, Vat Blue 4, Vat Blue 20, Vat Brown 1 and Vat Brown 3.

摘要

尽管蒽醌类化合物和其他染料被广泛使用且人类有大量接触的潜在风险,但关于它们的遗传毒性数据却很有限。在本研究中,选取了16种蒽醌类化合物和1种偶氮染料(溶剂红1),采用胸苷激酶(tk)基因座和微核(MN)分析方法,在L5178Y/TK(+/-)-3.7.2C小鼠淋巴瘤细胞中进行测试。其中6种染料与美国国家毒理学计划(NTP)啮齿动物生物测定中使用的染料来自同一批次。所使用的染料均为生产批次,因此纯度各不相同。分散蓝7、2-氨基蒽醌、1-氨基-2-甲基蒽醌、分散蓝3和分散红11具有遗传毒性(分别诱导1814个突变体/10⁶个存活细胞,存活13%时微核率为369个/1000个细胞;397个突变体/10⁶个存活细胞,存活21%时微核率为196个/1000个细胞;178个突变体/10⁶个存活细胞,存活51%时微核率为119个/1000个细胞;264个突变体/10⁶个存活细胞,存活15%时微核率为109个/1000个细胞)。活性蓝19具有弱致突变性(诱导144个突变体/10⁶个存活细胞,但存活13%时微核率仅为8个/1000个细胞)。还原黄4和溶剂红1在外源激活的情况下也具有致突变性(分别诱导300个突变体/10⁶个存活细胞,存活57%时微核率为18个/1000个细胞,以及100个突变体/10⁶个存活细胞,存活22%时微核率为16个/1000个细胞)。经激活后,1-硝基-2-甲基蒽醌的致突变性反应判定为不明确。某些化合物由于溶解度的限制,最大测试浓度受到限制。那些在溶解度极限下未诱导突变或细胞毒性的化学物质被单独分类。因不溶性未在外源未激活情况下评估但在激活情况下评估的化合物包括1-硝基-2-甲基蒽醌、溶剂红1和还原黄4。因在培养基中不溶而未在有或无S9激活情况下评估的化合物包括1-氨基-2,4-二溴蒽醌、D&C绿、分散蓝1、分散红60、还原蓝4、还原蓝20、还原棕1和还原棕3。

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