Effect of the hepatocarcinogenic peroxisome proliferator Wy-14,643 in vivo: no increase in ethane exhalation or hepatic conjugated dienes.

Exhalation of ethane and pentane was used to access lipid peroxidation in rats receiving the hepatocarcinogenic peroxisome proliferator Wy-14,643 at 0.1% in the diet. Wy-14,643 treatment from 23 to 345 days did not increase ethane or pentane exhalation. The lack of an increase in ethane exhalation from rats fed Wy-14,643 was not due to resistance to lipid peroxidation or increased metabolism of ethane since rats fed Wy-14,643 were sensitive to CCl4-induced increases in ethane exhalation and cleared exogenous ethane at rates similar to controls. Difference spectra of hepatic lipids extracted from control and Wy-14,643-treated rats showed peaks at 220 and 275 nm but no defined peak at 240 nm, the wavelength at which conjugated dienes in peroxidized lipids absorb. In contrast, injection of CCl4 ip into control rats produced dose-dependent increases in ethane exhalation at 6.25 to 100 microliters/kg and increases in hepatic conjugated dienes and serum liver enzyme activities at 200 to 1000 microliters/kg. The lack of increased ethane and pentane exhalation in combination with no detectable increase in hepatic conjugated dienes argues against increased hepatic lipid peroxidation in rats receiving a hepatocarcinogenic dose of Wy-14,643.