An initiation-promotion protocol was used to test the hypothesis that unleaded
gasoline (UG) vapor acts as a liver
tumor promoter in female mice under exposure conditions in which UG was hepatocarcinogenic in a
cancer bioassay. Twelve day old female B6C3F1 mice were injected with
N-nitrosodiethylamine (DEN, 5 mg/kg, i.p.) or vehicle. Starting at 5-7 weeks of age, mice were exposed by inhalation 6 h/day, 5 days/week for 13 weeks to 0 or 2039 p.p.m. of
PS-6 blend UG, the same
gasoline blend used in the
cancer bioassay. Putative preneoplastic lesions in liver, characterized mainly as basophilic foci in H&E-stained liver sections, were found exclusively in mice treated with DEN. While similar numbers of altered hepatic foci were found in DEN-initiated mice treated with 0 or 2039 p.p.m. UG, UG treatment significantly increased both the mean volume (3.2-fold) and the volume fraction (3.6-fold) of the foci. To determine if UG induced CYP2B, a subfamily of
cytochrome P450 commonly induced by liver
tumor promoters in rodents,
pentoxyresorufin-O-dealkylase (
PROD) activity was assayed in hepatic microsomes derived from the above livers. UG vapor increased hepatic
PROD activity approximately 8-fold, while increasing
cytochrome P450 content only approximately 30%. To ascertain if a more recent blend of UG, API 91-1, would have similar
biological effects as
PS-6, female B6C3F1 mice were gavaged for 3 days with
corn oil or 1800 mg/kg/day
PS-6 or API 91-1 blend UG.
PS-6 and API 91-1 blend UG induced similar increases in relative liver weight (approximately 25%),
PROD activity (approximately 9-fold) and hepatocyte labeling index (approximately 8-fold) relative to controls. These data demonstrate that
PS-6 blend UG vapor promotes preneoplastic lesions and induces CYP2B in female mouse liver under exposure conditions in which it causes liver
tumors, and suggest that a more recent blend of UG may have similar effects.