Biotransformation of carbon tetrachloride and lipid peroxidation promotion by liver nuclear preparations from different animal species.
Liver nuclear preparations from male Syrian Golden hamster (SG); C3H mice and Sprague-Dawley (SD) rats were able to biotransform CCl4 to CHCl3. That ability was not NADPH dependent and proceeded to an equal extent under N2 or air. Studies in more detail with C3H mice preparations revealed that only one of the processes was of an enzymatic nature and that it was inhibited by 1 mM EDTA. There was a correlation between liver nuclear ability to biotransform CCl4 to CHCl3 in the species tested and their liver carcinogenic response to CCl4. That correlation was not observed when biotransformation was studied using liver slices instead of liver nuclei. Liver nuclear preparations from the 3 species were able to promote a lipid peroxidation (LP) process in the presence of CCl4. The process was fully NADPH dependent in the case of SG and SD preparations but not in C3H mice. Study of the process in detail in the case of C3H mice shows that in that case LP was heat and EDTA sensitive, particularly in the absence of NADPH. There was no correlation between the intensity of CCl4 promoted LP either in liver nuclear or liver slices preparations in the 3 species tested and their carcino genic response to CCl4. Results might suggest that LP does not determine or rate limit the process of cancer development by CCl4 but do not exclude its participation in a given stage of the overall process.
Centro de Investigaciones Toxicológicas CITEFA/CONICET, Buenos Aires, Argentina.
G D
GD
Castro
M I
MI
Díaz Gómez
J A
JA
Castro
D000818:Animals; D001711:Biotransformation; D002251:Carbon Tetrachloride / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity; D002467:Cell Nucleus / Q000378:metabolism*; D002725:Chloroform / Q000378:metabolism; D006224:Cricetinae; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008809:Mice, Inbred C3H; D010420:Pentanes / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D010420:Pentanes; C033353:pentane; D002725:Chloroform; D002251:Carbon Tetrachloride