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2918378 
Journal Article 
The Effect Of Carbon Tetrachloride On Heme Components And Ethylmorphine Metabolism In Rat Liver Microsomes 
Greene, FE; Stripp, B; Gillette, JR 
1969 
Yes 
Biochemical Pharmacology
ISSN: 0006-2952
EISSN: 1873-2968 
NIOSH/00161176 
18 
6 
1531-1533 
The effect of carbon-tetrachloride (56235) (CCl4) on heme components and ethylmorphine (76584) metabolism was investigated in liver microsomes from the rat. Male Osborne-Mendel-rats were used in the experiments. Animals received a single 2.5 milliliter per kilogram (ml/kg) dose by stomach tube of CCl4. At various times after dosing, animals were sacrificed, livers removed and homogenized, and the homogenate centrifuged to isolate the microsomal pellet which was resuspended in a Tris/hydrochloric-acid/potassium-chloride solution. The amounts of cytochrome-P-450 (9035512), cytochrome-P-420 (9035498), cytochrome-b5 (9035396), and total heme were determined by spectrophotometric methods. Ethylmorphine metabolism was studied in mixtures containing the microsomes and an ethylmorphine concentration of 1 millimolar incubated for 10 minutes at 37 degrees-C. Results showed that the inhibitory effect of CCl4 on the microsomal demethylation of ethylmorphine parallels a decrease in the amount of cytochrome-P-450. This decrease in cytochrome-P-450 was closely related to the decrease in the content of heme. During the first 12 hours after dosing, no significant change in cytochrome-b5 occurred. After 24 hours, however, a pronounced decrease was observed. Cytochrome-P-420 was measurable only after 24 hours. The authors conclude that CCl4 caused a direct loss of cytochrome-P-450 as a heme component rather than a functional alteration.