Promotion of preneoplastic lesions and induction of CYP2B by unleaded gasoline vapor in female B6C3F1 mouse liver.
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.
Standeven
A M
AM
Department of Experimental Pathology and Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709.
Goldsworthy
T L
TL
D000818:Animals; D019362:Cytochrome P-450 CYP2B1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004052:Diethylnitrosamine; D004790:Enzyme Induction; D005260:Female; D005742:Gasoline; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000096:biosynthesis*; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000201:enzymology; D012965:Sodium Chloride
D005742:Gasoline; D004052:Diethylnitrosamine; D012965:Sodium Chloride; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019362:Cytochrome P-450 CYP2B1