Hyperketonaemia markedly modulates the metabolic activation of chemical carcinogens.
Male Wistar albino rats were rendered hyperketonaemic by oral administration of medium chain triacylglycerols or by a single intraperitoneal injection of the diabetogenic agent streptozotocin. Hepatic post-mitochondrial preparations from these animals were employed as activation systems in the Ames mutagenicity test. Activation systems from both groups of hyperketonaemic rats were more efficient than those of control rats in metabolically converting the precarcinogens Glu-P-1, Trp-P-1, Trp-P-2, N-nitrosopiperidine and N-nitrosopyrrolidine to mutagens. In contrast, when 2-aminofluorene was used as the precarcinogen, the preparations from the hyperketonaemic animals were less efficient than controls in activating this carcinogen. In all cases, the preparations from streptozotocin-treated rats displayed a more pronounced effect than those from triacylglycerol-treated rats, possibly reflecting the greater extent of hyperketonaemia in the former group. It is concluded that hyperketonaemia modulates the bioactivation of chemical carcinogens.
Barnett
C R
CR
Department of Biochemistry, University of Surrey, Guildford, U.K.
Flatt
P R
PR
Ioannides
C
C
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000097:blood; D000818:Animals; D001711:Biotransformation; D002273:Carcinogens; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003920:Diabetes Mellitus / Q000201:enzymology; D005449:Fluorenes / Q000494:pharmacology; D006885:Hydroxybutyrates / Q000097:blood; D007659:Ketones / Q000097:blood*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009153:Mutagens; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin; D014280:Triglycerides / Q000633:toxicity*
D000090:Acetoacetates; D002273:Carcinogens; D005449:Fluorenes; D006885:Hydroxybutyrates; D007659:Ketones; D009153:Mutagens; D014280:Triglycerides; C012177:2-aminofluorene; C016635:acetoacetic acid; D013311:Streptozocin; D003577:Cytochrome P-450 Enzyme System; D020155:3-Hydroxybutyric Acid