Embryonic turkey liver: activities of biotransformation enzymes and activation of DNA-reactive carcinogens.
Avian embryos are a potential alternative model for chemical toxicity and carcinogenicity research. Because the toxic and carcinogenic effects of some chemicals depend on bioactivation, activities of biotransformation enzymes and formation of DNA adducts in embryonic turkey liver were examined. Biochemical analyses of 22-day in ovo turkey liver post-mitochondrial fractions revealed activities of the biotransformation enzymes 7-ethoxycoumarin de-ethylase (ECOD), 7-ethoxyresorufin de-ethylase (EROD), aldrin epoxidase (ALD), epoxide hydrolase (EH), glutathione S-transferase (GST), and UDP-glucuronyltransferase (GLUT). Following the administration of phenobarbital (24 mg/egg) on day 21, enzyme activities of ECOD, EROD, ALD, EH and GLUT, but not of GST, were increased by two-fold or higher levels by day 22. In contrast, acute administration of 3-methylcholanthrene (5 mg/egg) induced only ECOD and EROD activities. Bioactivation of structurally diverse pro-carcinogens was also examined using (32)P-postlabeling for DNA adducts. In ovo exposure of turkey embryos on day 20 of gestation to 2-acetylaminofluorene (AAF), 4,4'-methylenebis(2-chloroaniline) (MOCA), benzo[a]pyrene (BaP), and 2-amino-3,8-dimethylimidazo[4,5- f]quinoxaline (MeIQx) resulted in the formation of DNA adducts in livers collected by day 21. Some of the DNA adducts had (32)P-postlabeling chromatographic migration patterns similar to DNA adducts found in livers from Fischer F344 rats exposed to the same pro-carcinogens. We conclude that 21-day embryonic turkey liver is capable of chemical biotransformation and activation of genotoxic carcinogens to form DNA adducts. Thus, turkey embryos could be utilized to investigate potential chemical toxicity and carcinogenicity.
Perrone
Carmen E
CE
Department of Pathology, New York Medical College,Valhalla, NY 10595, USA. Carmen_Perrone@nymc.edu.
Ahr
Hans-Juergen
HJ
Duan
Jian Dong
JD
Jeffrey
Alan M
AM
Schmidt
Ulrich
U
Williams
Gary M
GM
Enzmann
Harald H
HH
D015073:2-Acetylaminofluorene / Q000378:metabolism / Q000633:toxicity; D000826:Animal Testing Alternatives; D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism* / Q000633:toxicity; D018736:DNA Adducts / Q000032:analysis / Q000378:metabolism*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000201:enzymology*; D004798:Enzymes / Q000378:metabolism*; D005260:Female; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000201:enzymology*; D008748:Methylcholanthrene / Q000378:metabolism / Q000633:toxicity; D008753:Methylenebis(chloroaniline) / Q000378:metabolism / Q000633:toxicity; D010634:Phenobarbital; D010761:Phosphorus Radioisotopes; D011810:Quinoxalines / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D014421:Turkey
D002273:Carcinogens; D018736:DNA Adducts; D004798:Enzymes; D010761:Phosphorus Radioisotopes; D011810:Quinoxalines; D001564:Benzo(a)pyrene; D008753:Methylenebis(chloroaniline); D008748:Methylcholanthrene; D015073:2-Acetylaminofluorene; D010634:Phenobarbital; C045421:3,4,8-trimethylimidazo(4,5-f)quinoxalin-2-amine