Polycyclic hydrocarbon‐produced toxicity, transformation, and chromosomal aberrations as a function of aryl hydrocarbon hydroxylase activity in cell cultures

Polycyclic hydrocarbon‐produced toxicity, transformation, and chromosomal aberrations as a function of aryl hydrocarbon hydroxylase activity in cell cultures
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细胞培养物中多环烃产生的毒性、转化和染色体畸变与芳烃羟化酶活性的关系

DOI:
10.1002/ijc.2910090223
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发表时间:
1972
影响因子:
6.4
通讯作者:
D. Nebert
D. Nebert
中科院分区:
医学1区
文献类型:
--
作者:
W. Benedict;J. Gielen;D. Nebert

文献摘要

被引文献

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苯巴比妥可阻止苯并[a]芘单独对培养的胎鼠肝细胞的细胞毒性作用。苯并[a]芘对HTC、A9或HeLa细胞(其中芳烃羟化酶活性不存在或非常低)没有毒性;然而,苯并[a]芘对这三种在苯巴比妥存在下与肝细胞一起生长的已建立细胞系中的每一种都具有细胞毒性。多环烃产生的细胞毒性与染色单体断裂相关,而非整倍性与仓鼠传代培养物的恶性转化更密切相关。苯并[a]蒽或a-萘酮竞争性地抑制其他多环烃的羟基化,例如致癌物7,12-二甲基苯并[a]蒽或苯并[a]芘。在用7,12-二甲基苯并[a]蒽处理之前、期间和之后,将胎仓鼠次级细胞暴露于过量的苯并[a]蒽可防止发生恶性细胞转化。
The cytotoxic effect of benzo[a]pyrene alone in fetal rat hepatocytes in culture is prevented by phenobarbital. Benzo[a]pyrene is not toxic to HTC, A9, or HeLa cells in which aryl hydrocarbon hydroxylase activity is either absent or very low; however, benzo[a]pyrene is cytotoxic to each of these three established cell lines grown together with the liver cells in the presence of phenobarbital. Polycyclic hydrocarbon‐produced cytotoxicity is associated with chromatid breaks, whereas aneuploidy is more closely correlated with malignant transformation of hamster secondary cultures. Benz[a]anthracene or a‐naphthoflavone competitively inhibits the hydroxylation of other polycyclic hydrocarbons such as the carcinogens 7,12‐dimethylbenz[a]anthracene or benzo[a]pyrene. The exposure of fetal hamster secondary cells to excessive amounts of benz[a]anthracene prior to, during, and following treatment with 7,12‐dimethylbenz[a]anthracene prevents malignant cell transformation from occurring.