Comparative effects of quinoline and 8-hydroxyquinoline on glutathione levels, DNA fragmentation and enzvme induction in cultured rat hepatocytes.
Tirmenstein-MA; Snawder-JE; Plews-PI; Toraason-M
Toxicologist 1994 Mar; 14(1):193
Quinoline and 8-hydroxyquinoline(8-HQ) are major industrial chemicals. Quinoline is also a constituent of automobile exhaust, tobacco smoke and indoor air pollution. Studies have shown that quinoline is a hepatocarcinogen and potent mitogen in rats and mice. 8-HQ, however, failed to induce hepatic carcinogenesis when tested in rodent chronic boassays, and is not known to produce a mitogenic response in rat liver. The following study was conducted to assess the comparative effects of quinoline and 8-HQ on hepatocyte function. Exposure to quinoline for 3 hrs depleted hepatocyte glutathione (GSH) levels in a dose-dependent manner. The addition of 500 uM quinoline depleted GSH levels to about 60 % of control values after 3 hrs. Quinoline did not induce the formation of oxidized glutathione (GSSG) at the concentrations tested. Exposure to 500uM 8-HQ for 3 hrs also depleted hepatocyte GSH to about 70% of control values, but GSH loss could be accounted for by increases in GSSG levels. Lower concentrations of 8-HQ did not deplete glutathione levels at the 3 hr timepoint. Both compounds induced increases in single strand DNA breaks at selected concentrations as judged by alkaline elution analysis, but 8-HQ induced increases in DNA single-strand breaks were associated with cytotoxic concentrations of 8HQ. Hepatocytes cultured for 48 hrs and subsequently exposed to quinoline or 8-HQ exhibited increased levels of ornithine decarboxylase activity 4 hrs after the addition of the chemicals. The result of this study suggests that quinoline and 8-hydroxyquinoline have significantly different effects on hepatocyte function.
Laboratory-testing; Toxins; Toxicology; Toxic-effects; Exposure-assessment; Exposure-levels; DNA-damage; Bioassays; Industrial-emissions; Industrial-exposures; Hepatic-microsomal-enzymes; Liver-damage; Liver-enzymes; Liver-function
The Toxicologist. Society of Toxicology 33rd Annual Meeting, March 13-17, 1994, Dallas, Texas