Lowering effect of carbon tetrachloride on microsomal cytochrome P-450 of rat liver.

The lowering effect of carbon tetrachloride (CCl4) on the amount of hepatic microsomal cytochrome P-450 of male rats was studied in vitro. It was found that CCl4 added directly into the media containing microsomal supensions decreased the amount of cytochrome P-450 detectable by difference spectra at zero time of incubation. The incubation of the media with CCl4 at 37 degrees in an open system or in a closed system did not decrease the content of cytochrome P-450. As cytochrome P-420 was not detected in the addition of CCl4 lower than 10 mul, it was postulated that the decrease in the content of cytochrome P-450 was not due to its conversion to cytochrome P-420. The activity of NADPH-cytochrome c reductase was not affected by CCl4. The results indicate that the decrease of the amount of detectable cytochrome P-450 by CCl4 is due to the destruction of cytochrome P-450 and the binding of cytochrome P-450 with CCl4in a lower concentration of CCl4 and in addition it is due to the conversion of cytochrome P-420 from cytochrome P-450 in a higher concentration of CCl4.