BIOASSAY OF QUINOLINE, 5-FLUOROQUINOLINE, CARBAZOLE, 9-METHYLCARBAZOLE AND 9-ETHYLCARBAZOLE IN NEWBORN MICE

Quinoline and carbazole are among the more prevalent aza-arenes presen t as components of environmental pollutants. Both of these aza-arenes are hepatocarcinogenic to mice when administered in the diet. The hepa tocarcinogenic potential of quinoline is consistent with its mutagenic activity in Salmonella typhimurium TA100 and potential to induce unsc heduled DNA synthesis (UDS) in rat hepatocytes. Structure-activity stu dies with fluorinated quinolines indicate that the presence of a fluor ine 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 mumol to es tablish their relative tumorigenic activity. Liver tumours developed i n 60 and 90% of the male newborn mice treated with quinoline and 5-flu oroquinoline, respectively. The majority of liver tumours observed amo ng the quinoline-treated mice were classified as adenomas. In contrast , liver carcinomas developed in most of the male mice treated with 5-f luoroquinoline. Unlike the well established genotoxic potential of qui noline, there is limited evidence for carbazole having either genotoxi c or carcinogenic activity. Whereas carbazole is not mutagenic towards several strains of S. typhimurium, both 9-methylcarbazole and 9-ethyl carbazole are active as mutagens in S. typhimurium TA100. Carbazole, 9 -methylcarbazole and 9-ethylcarbazole were assayed in primary rat hepa tocytes to assess their relative potential to induce UDS in rat hepato cytes; only 9-ethylcarbazole did so. These carbazole derivatives were also assayed in newborn CD-1 mice at a total dose of 1.75 mumol. Neith er carbazole nor either of these 9-alkylcarbazoles produced a signific ant tumorigenic response in this bioassay system.