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淋巴细胞氚化胸腺嘧啶核苷试验中致癌物、致癌物类似物及代谢抑制剂的活性

Activity of carcinogens, carcinogen analogs, and metabolic inhibitors in the lymphocyte tritiated thymidine assay.

作者信息

Warren J R, Summerville J W

出版信息

J Natl Cancer Inst. 1980 Dec;65(6):1321-8.

PMID:6933277
Abstract

Inhibition of tritiated thymidine ([3H]dThd) incorporation into replicating DNA of concanavalin A (Con A)-stimulated C57BL/6J splenic lymphocytes has been further evaluated as an end point for rapid in vitro discrimination between carcinogenic and noncarcinogenic chemicals. Results of this evaluation include: a) Inhibition of [3H]dThd incorporation into DNA of Con A-stimulated cells clearly discriminated between known DNA-damaging chemical carcinogens (N-methyl-N-nitrosourea, 4-nitroquinoline 1-oxide, 4-(hydroxyamino)quinoline 1-oxide, benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, and benz[a]anthracene) and non-DNA-damaging metabolic inhibitors of replication (dimethyl sulfoxide, ethanol, hydroxyurea, cycloheximide, potassium cyanide, and oligomycin). b) Inhibition of [3H]dThd incorporation also discriminated between carcinogens and noncarcinogens in the two pairs 4-nitroquinoline 1-oxide versus quinoline-N-oxide, and benzo[a]pyrene versus pyrene. c) Inhibition of [3H]dThd incorporation did not quantitatively discriminate between the structurally related strong carcinogen dimethylbenz[a]anthracene, the weak carcinogen benz[a]anthracene, and the equivocal carcinogens anthracene and phenanthrene. d) Inhibition of [3H]dThd incorporation was not a sensitive in vitro end point for the carcinogenic hypolipidemic drug 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid (Wy-14,643).

摘要

将氚标记胸腺嘧啶核苷([3H]dThd)掺入伴刀豆球蛋白A(Con A)刺激的C57BL/6J脾淋巴细胞复制DNA的抑制作用,已被进一步评估作为体外快速区分致癌和非致癌化学物质的一个终点。该评估结果包括:a)将[3H]dThd掺入Con A刺激细胞DNA的抑制作用,能明确区分已知的DNA损伤化学致癌物(N-甲基-N-亚硝基脲、4-硝基喹啉1-氧化物、4-(羟基氨基)喹啉1-氧化物、苯并[a]芘、7,12-二甲基苯并[a]蒽和苯并[a]蒽)与非DNA损伤的复制代谢抑制剂(二甲基亚砜、乙醇、羟基脲、环己酰亚胺、氰化钾和寡霉素)。b)[3H]dThd掺入的抑制作用也能区分4-硝基喹啉1-氧化物与喹啉-N-氧化物、苯并[a]芘与芘这两对物质中的致癌物和非致癌物。c)[3H]dThd掺入的抑制作用在结构相关的强致癌物二甲基苯并[a]蒽、弱致癌物苯并[a]蒽以及可疑致癌物蒽和菲之间,未进行定量区分。d)[3H]dThd掺入的抑制作用,对于致癌性降血脂药物4-氯-6-(2,3-二甲基苯胺基)-2-嘧啶硫代乙酸(Wy-14,643)而言,并非一个敏感的体外终点。

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