Increased stability of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene through interaction with subcellular fractions of rat liver.
The rate of hydrolysis of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene (BPDE) to tetrahydroxy derivatives (tetrols) in the presence of various subcellular fractions of rat liver was investigated. Microsomes and nuclei increased the half-life of BPDE in a concentration-dependent manner whereas cytosol had no such effect. The presence of 1 mg microsomal protein/ml increased the half-life of BPDE from 4 to 60 min at 22 degrees C and from 1.5 to 20 min at 37 degrees C. Nuclei equivalent of 500 micrograms DNA/ml increased the half-life from 1.9 to 3.6 min at 37 degrees C. Liposomes prepared from microsomal lipids mimicked the effect of microsomes indicating that BPDE is stabilized primarily by interacting with lipids. The significance of these interactions for the stability of BPDE in an intact cell system was evaluated by using isolated hepatocytes. In these cells the half-life of BPDE was substantially shorter (1 min at 5 X 10(6) cells/ml) than in buffer (3 min). However, hydrolysis of BPDE to tetrols was a minor reaction (less than or equal to 3% of added BPDE at a cell density greater than or equal to 5 X 10(6) cells/ml) and the main route of elimination (greater than or equal to 75%) was through conjugation with glutathione.
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002250:Carbon Radioisotopes; D002273:Carcinogens / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004101:Dihydroxydihydrobenzopyrenes / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006207:Half-Life; D006868:Hydrolysis; D007700:Kinetics; D008081:Liposomes; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D002250:Carbon Radioisotopes; D002273:Carcinogens; D004101:Dihydroxydihydrobenzopyrenes; D008081:Liposomes; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D005978:Glutathione