Matsumoto M, Ando M
Environmental Health Sciences Division, National Institute for Environmental Studies, Ibaraki, Japan.
Environ Mol Mutagen. 1991;17(2):104-11. doi: 10.1002/em.2850170207.
3-Chlorodibenzofuran was the only markedly mutagenic isomer among the four monochlorodibenzofurans. Although it was mutagenic even in the absence of 9,000g supernatant fraction (S9) of rat liver, it was further activated by the addition of S9. Metabolic activation of this compound in mutagenicity was studied using liver S9s and cell fractions which were prepared from rats treated with two inducers. 1,1-Dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) was used as an inducer of phenobarbital inducible cytochrome P-450, and beta-naphthoflavone (beta NF) was used as an inducer of 3-methylcholanthrene inducible cytochrome P-448. S9, microsomal, mitochondrial, and cytosolic fractions were obtained from four groups of rats, i.e., untreated, DDE treated, beta NF treated, and DDE and beta NF treated groups. Mutagenicity was tested using Salmonella typhimurium tester strain TA98, because this strain is more sensitive to 3-chlorodibenzofuran than strain TA100. This experiment showed that 3-chlorodibenzofuran was activated most highly by beta NF-induced microsomes. However, it was also activated by the cytosolic fraction. Moreover, it was highly activated in rat livers which were not treated with inducers. The activity of aryl hydrocarbon hydroxylase (AHH) of each fraction was measured. AHH did not always become an index of the metabolic activation of 3-chlorodibenzofuran. This study showed that 3-chlorodibenzofuran is activated not only by cytochrome P-448, which is induced by 3-methylcholanthrene type inducers, but also by the enzymes existing in normal rat liver. This result suggests a risk of manifestation of its toxicity to normal animals.
3-氯二苯并呋喃是四种一氯二苯并呋喃中唯一具有明显致突变性的异构体。尽管它在没有大鼠肝脏9000g上清液组分（S9）的情况下也具有致突变性，但添加S9后它会进一步被激活。使用由两种诱导剂处理的大鼠制备的肝脏S9和细胞组分研究了该化合物在致突变性方面的代谢激活作用。1,1-二氯-2,2-双（对氯苯基）乙烯（DDE）用作苯巴比妥诱导的细胞色素P-450的诱导剂，β-萘黄酮（βNF）用作3-甲基胆蒽诱导的细胞色素P-448的诱导剂。从四组大鼠中获得S9、微粒体、线粒体和胞质组分，即未处理组、DDE处理组、βNF处理组以及DDE和βNF处理组。使用鼠伤寒沙门氏菌测试菌株TA98测试致突变性，因为该菌株对3-氯二苯并呋喃比菌株TA100更敏感。该实验表明，3-氯二苯并呋喃被βNF诱导的微粒体激活程度最高。然而，它也被胞质组分激活。此外，它在未用诱导剂处理的大鼠肝脏中也被高度激活。测量了每个组分的芳烃羟化酶（AHH）活性。AHH并不总是成为3-氯二苯并呋喃代谢激活的指标。这项研究表明，3-氯二苯并呋喃不仅被3-甲基胆蒽型诱导剂诱导的细胞色素P-448激活，而且还被正常大鼠肝脏中存在的酶激活。这一结果表明其对正常动物表现出毒性的风险。
