Bioassay of quinoline, 5-fluoroquinoline, carbazole, 9-methylcarbazole and 9-ethylcarbazole in newborn mice.
Bioassay of quinoline, 5-fluoroquinoline, carbazole, 9-methylcarbazole and 9-ethylcarbazole in newborn mice.
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新生小鼠体内喹啉、5-氟喹啉、咔唑、9-甲基咔唑和 9-乙基咔唑的生物测定。
DOI：
10.1016/0278-6915(93)90141-k
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
LaVoie,EJ
中科院分区：
文献类型：
--
作者：
Weyand,EH;Defauw,J;McQueen,CA;Meschter,CL;Meegalla,SK;LaVoie,EJ
喹啉和咔唑是环境污染物中最常见的氮杂芳烃。当在饮食中施用这两种氮杂芳烃时，这两种氮杂芳烃都会对小鼠产生肝癌作用。喹啉的肝癌潜力与其对鼠伤寒沙门氏菌 TA100 的诱变活性以及在大鼠肝细胞中诱导非计划性 DNA 合成 (UDS) 的潜力一致。氟化喹啉的结构活性研究表明，喹啉 5 位氟原子的存在可能会抑制解毒并导致遗传毒性效力增强。在新生 CD-1 小鼠中以 1.75 μmol 的总剂量测定喹啉和 5-氟喹啉，以确定它们的相对致瘤活性。接受喹啉和 5-氟喹啉治疗的雄性新生小鼠中，分别有 60% 和 90% 出现肝脏肿瘤。在喹啉治疗的小鼠中观察到的大多数肝脏肿瘤被归类为腺瘤。相比之下，大多数接受 5-氟喹啉治疗的雄性小鼠都出现了肝癌。与喹啉的潜在遗传毒性不同，咔唑具有遗传毒性或致癌活性的证据有限。而咔唑对 S 的几种菌株没有诱变性。对于鼠伤寒沙门氏菌，9-甲基咔唑和 9-乙基咔唑均具有作为鼠伤寒沙门氏菌的诱变剂的活性。鼠伤寒TA100。在原代大鼠肝细胞中测定咔唑、9-甲基咔唑、9-乙基咔唑，以评估它们在大鼠肝细胞中诱导 UDS 的相对潜力；只有9-乙基咔唑可以做到这一点。这些咔唑衍生物还在新生 CD-1 小鼠中进行了检测，总剂量为 1.75 μmol。在该生物测定系统中，咔唑和这些 9-烷基咔唑均未产生显着的致瘤反应。
Quinoline and carbazole are among the more prevalent aza-arenes present as components of environmental pollutants. Both of these aza-arenes are hepatocarcinogenic to mice when administered in the diet. The hepatocarcinogenic potential of quinoline is consistent with its mutagenic activity inSalmonella typhimuriumTA100 and potential to induce unscheduled DNA synthesis (UDS) in rat hepatocytes. Structure-activity studies with fluorinated quinolines indicate that the presence of a fluorine atom at the 5-position of quinoline may inhibit detoxification and result in enhanced genotoxic potency. Quinoline and 5-fluoroquinoline were assayed in newborn CD-1 mice at a total dose of 1.75 μmol to establish their relative tumorigenic activity. Liver tumours developed in 60 and 90% of the male newborn mice treated with quinoline and 5-fluoroquinoline, respectively. The majority of liver tumours observed among the quinoline-treated mice were classified as adenomas. In contrast, liver carcinomas developed in most of the male mice treated with 5-fluoroquinoline. Unlike the well established genotoxic potential of quinoline, there is limited evidence for carbazole having either genotoxic or carcinogenic activity. Whereas carbazole is not mutagenic towards several strains ofS. typhimurium, both 9-methylcarbazole and 9-ethylcarbazole are active as mutagens inS. typhimuriumTA100. Carbazole, 9-methylcarbazole 9-ethylcarbazole were assayed in primary rat hepatocytes to assess their relative potential to induce UDS in rat hepatocytes; only 9-ethylcarbazole did so. These carbazole derivatives were also assayed in newborn CD-1 mice at a total dose of 1.75 μmol. Neither carbazole nor either of these 9-alkylcarbazoles produced a significant tumorigenic response in this bioassay system.