Identification of hepatic mitogenic and cytochrome P-450-inducing fractions of unleaded gasoline in B6C3F1 mice
- Chemical Industry Institute of Toxicology, Research Triangle Park, NC (United States)
Unleaded gasoline (UG), a complex mixture of over 300 hydrocarbons, induced liver tumors selectively in female mice and exhibited liver tumor promoting activity. UG also induced cell proliferation and cytochrome P-450-related enzyme activities in mouse liver, properties commonly associated with liver tumor promoters. To determine if the mitogenic and/or cytochrome P-450-inducing properties of UG reside in individual fractions of UG, UG was separated into four fractions on the basis of boiling point (BP): fraction1, BP <66{degrees}C; fraction 2, 66{degrees}C < BP < 100{degrees}C; fraction 3, 100{degrees}C < BP < 132{degrees}C; fraction 4, BP > 132{degrees}C. Fractions 1 and 2 were combined to form {open_quotes}light UG{close_quotes}, and fractions 3 and 4 were combined to form {open_quotes}heavy UG{close_quotes}. Female 86C3F1 mice were implanted with osmotic pumps containing 5-bromo-2{prime}-deoxyuridine (BrdU) on d 1, treated by intragastric intubation with corn oil or 3000 mg/kg/d of light, heavy, or whole UG on d 2-4, and euthanized on d 5. Pentoxyresorufin O-dealkylase (PROD) and ethoxyresorufin O-deethylase (EROD) activities were assayed in hepatic microsomes, and hepatocyte BrdU labeling index (LI) was determined in liver sections. Whole UG and heavy UG caused comparable increased in hepatic PROD and EROD activities and the hepatocyte LI. Light UG caused relatively small increased in hepatic PROD and EROD activities and did not increase the hepatocyte LI. When fractions 3 and 4 were tested separately in the above treatment protocol, both fractions strongly induced hepatic PROD and weakly induced hepatic EROD activities. However, only fraction 3 increased the hepatocyte LI. To isolate mitogenic components in fraction 3, equimolar doses of individual chemicals in fraction 3 were tested in the above treatment protocol. 28 refs., 4 tabs.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 83120
- Journal Information:
- Journal of Toxicology and Environmental Health, Vol. 43, Issue 2; Other Information: PBD: 1994
- Country of Publication:
- United States
- Language:
- English
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