Sequential 2-acetylaminofluorene--phenobarbital exposure induces a cytosolic aldehyde dehydrogenase during rat hepatocarcinogenesis.
A significant change in hepatic aldehyde dehydrogenase activity has been observed in normal Sprague-Dawley rat liver during the promotion phase of hepatocarcinogenesis induced by brief feeding of 2-acetylaminofluorene (2-AAF) followed by tumor promotion using dietary phenobarbital (PB) exposure. Animals receiving only 2-AAF or PB do not possess this new aldehyde dehydrogenase activity. The phenotype is characterized by the appearance of a new cytosolic isozyme kinetically, electrophoretically and immunochemically distinct from the normal liver aldehyde dehydrogenase isozymes and from aldehyde dehydrogenases inducible in 2-AAF-induced hepatomas. The new isozyme is NAD-dependent, disulfiram-sensitive and cross-reacts with antiserum to a normal liver aldehyde dehydrogenase inducible in several lines of rats by PB. However, the population of animals used in this study has been shown previously to be non-responsive to aldehyde dehydrogenase induction by dietary PB. Since no animals receiving only PB express this new isozyme, the carcinogen must play a significant role in its induction. Moreover, that not all animals receiving carcinogen and promoter possess the phenotype suggests this carcinogen/promoter interaction has a genetic basis.
D015073:2-Acetylaminofluorene / Q000008:administration & dosage*; D000445:Aldehyde Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D000818:Animals; D003043:Cocarcinogenesis; D004334:Drug Administration Schedule; D004790:Enzyme Induction; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008113:Liver Neoplasms / Q000139:chemically induced*; D008297:Male; D010634:Phenobarbital / Q000008:administration & dosage*; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains
D015073:2-Acetylaminofluorene; D000445:Aldehyde Oxidoreductases; D010634:Phenobarbital