A comparison of the capacity of fetal and adult liver, lung, and brain to convert polycyclic aromatic hydrocarbons to mutagenic and cytotoxic metabolites in mice and rats.
A comparison of the capacity of fetal and adult liver, lung, and brain to convert polycyclic aromatic hydrocarbons to mutagenic and cytotoxic metabolites in mice and rats.
复制标题
比较小鼠和大鼠胎儿和成人肝脏、肺和大脑将多环芳烃转化为致突变和细胞毒性代谢物的能力。
DOI：
10.1016/0041-008x(79)90288-6
复制
发表时间：
1979
影响因子：
3.8
通讯作者：
A. H. Jones
中科院分区：
文献类型：
--
作者：
M. Juchau;J. DiGiovanni;M. Namkung;A. H. Jones
大鼠胎脑组织匀浆的上清液经9000g离心10min后，制备的S-9组分对7，12-二甲基苯并(A)蒽具有较强的转化能力，可转化为对鼠伤寒沙门氏菌测试菌株TA-98、TA-100和TA-1538具有诱变作用的代谢物。同一组织在将苯并(A)芘或N-2-荧基乙酰胺转化为诱变代谢物方面只有最低限度的活性或不活跃。小鼠胎脑组织对三种前致癌物的生物激活几乎都不活跃，但小鼠胎肺组织产生的诱变剂活性比7，12-二甲基苯(A)菲的本底高五到九倍。小鼠胎肝和胎脑组织也能催化这三种诱变剂转化为细胞毒性中间体，而大鼠胎肝和胎脑组织则未观察到这种现象。高压液相色谱分析表明，胎鼠脑组织在将7，12-二甲基苯并(A)蒽转化为含氧代谢产物方面非常活跃，而大鼠胎脑组织仅表现出极低的活性。层析图谱还表明，在大鼠和小鼠的S-9组分存在下，形成了不同的代谢物。这些数据与先前观察到的多环烃经胎盘肿瘤易感性的物种差异与这些化合物的靶器官生物转化的差异有关。
Preparations of S-9 (supernatant fractions of tissue homogenates centrifuged at 9000g for 10 min) fractions from the fetal brains of rats displayed a high capacity to convert 7,12-dimethylbenz(a)anthracene to metabolites mutagenic to Salmonella typhimurium tester strains TA-98, TA-100, and TA-1538. The same tissue was only minimally active or inactive in converting benzo(a)pyrene or N-2-fluorenylacetamide to mutagenic metabolites. Fetal brain tissues of mice were virtually inactive with respect to the bioactivation of each of the three procarcinogens but fetal pulmonary tissues of mice produced mutagen-generating activities that were five- to ninefold above background with respect to 7,12-dimethylbenz(a)anthracene. Fetal hepatic and brain tissues of mice also catalyzed the conversion of each of the three promutagens to cytotoxic intermediates but this phenomenon was not observed with fetal hepatic or brain tissues of rats. Analyses with high-pressure liquid chromatography demonstrated that brain tissues of fetal mice were very active in converting 7,12-dimethylbenz(a)anthracene to oxygenated metabolites whereas the fetal brain tissues of rats were only minimally active. The chromatographic patterns observed also indicated that different metabolites were formed in the presence of S-9 fractions from rats vs mice. The data are consistent with the hypothesis that the previously observed species difference in susceptibility to transplacental tumorigenesis by polycyclic hydrocarbons is related to differences in target organ biotransformation of these compounds.