Loss of tumor-promoting activity of unleaded gasoline in N-nitrosodiethylamine-initiated ovariectomized B6C3F1 mouse liver

Carcinogenesis
G J MoserT L Goldsworthy

Abstract

Unleaded gasoline (UG) vapor (2056 ppm) increased the incidence of liver tumors in a chronic bioassay and exhibited tumor-promoting activity in N-nitrosodiethylamine (DEN)-initiated female mouse liver. Estrogen inhibited mouse liver tumor development and the hepatocarcinogenic and tumor-promoting dose of UG produced uterine changes suggestive of estrogen antagonism. To directly test the hypothesis that UG-induced tumor-promoting ability is secondary to its interaction with the mouse liver tumor inhibitor, estrogen, we compared the tumor-promoting ability of UG in ovariectomized (Ovex) mice with the hepatic tumor-promoting ability of UG in intact mice. Ovaries were surgically removed at 4 weeks of age. Exposure to wholly vaporized UG (2018 ppm) under bioassay and tumor-promoting conditions began at 8 weeks of age. After 4 months of exposure, UG increased relative liver weight and hepatic microsomal cytochrome P450 pentoxyresourfin-O-dealkylase and ethoxyresorufin-O-deethylase activity to a similar extent in intact and Ovex mice. Non-focal hepatocyte proliferation, as measured by the incorporation of bromo-deoxyuridine, was not changed by UG exposure and was similar in all treatment groups. After 4 months of exposure to DEN-initi...Continue Reading

Citations

Sep 29, 2015·Critical Reviews in Toxicology·Kenneth T Bogen, Jacqueline M Heilman
Mar 15, 2003·Risk Analysis : an Official Publication of the Society for Risk Analysis·Gary L Ginsberg
Mar 27, 2001·Japanese Journal of Cancer Research : Gann·T NakataniA Ito

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