Bioassay of quinoline, 5-fluoroquinoline, carbazole, 9-methylcarbazole and 9-ethylcarbazole in newborn mice.
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 in Salmonella typhimurium TA100 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 mumol 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 of S. typhimurium, both 9-methylcarbazole and 9-ethylcarbazole are active as mutagens in S. typhimurium TA100. Carbazole, 9-methylcarbazole and 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 mumol. Neither carbazole nor either of these 9-alkylcarbazoles produced a significant tumorigenic response in this bioassay system.
Weyand
E H
EH
Rutgers, State University of New Jersey, College of Pharmacy, Department of Pharmaceutical Chemistry, Piscataway 08855-0789.
Defauw
J
J
McQueen
C A
CA
Meschter
C L
CL
Meegalla
S K
SK
LaVoie
E J
EJ
D000818:Animals; D000831:Animals, Newborn; D001681:Biological Assay; D002227:Carbazoles / Q000032:analysis / Q000633:toxicity*; D002273:Carcinogens / Q000032:analysis / Q000633:toxicity*; D005260:Female; D008099:Liver / Q000737:chemistry*; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009153:Mutagens / Q000032:analysis / Q000633:toxicity*; D011804:Quinolines / Q000032:analysis / Q000633:toxicity; D013329:Structure-Activity Relationship
D002227:Carbazoles; D002273:Carcinogens; D009153:Mutagens; D011804:Quinolines; C041514:carbazole; C082975:5-fluoroquinoline; C038545:N-methylcarbazole; C037219:quinoline