Genetically mediated induction of drug-metabolizing enzymes associated with congenital defects in the mouse

G H Lambert, D W Nebert


Various polycyclic aromatic compounds induce certain monooxygenase activities, including aryl hydrocarbon (benzo[a]pyrene) hydroxylase (EC, and cytochrome P1-450 in the liver and many nonhepatic tissues of the mouse. This induction process is controlled by the Ah locus. Genetic differences that have been shown in the past to be associated with the Ah locus include an increased susceptibility to chemical carcinogenesis, mutagenicity in vitro, and drug toxicity--manifested as hepatic necrosis, aplastic anemia, or shortened survival time. Pregnant mice received a single injection of 3-methylcholanthrene or 7,12-dimethylbenz[a] anthracene between day 5 and day 13 of gestation, and the uterine contents were examined on day 18. Striking increases were observed in the incidence of MC-1 and DMBA-induced resorptions and congenital malformations in the aromatic hydrocarbon "responsive" C57BL/6N inbred strain, and of DMBA-induced resorptions in the "responsive" C3H/HeN and BALB/cAnN strains--when compared with the similarly treated genetically "nonresponsive" AKR/N strain. These data suggest but do not prove that an association exists between the Ah locus and developmental toxicity, i.e., teratogenesis. Although numerous terato...Continue Reading


Jan 1, 1982·Teratogenesis, Carcinogenesis, and Mutagenesis·A G Fantel
Oct 1, 1995·Developmental Dynamics : an Official Publication of the American Association of Anatomists·B D AbbottG H Perdew
Oct 1, 1995·Developmental Dynamics : an Official Publication of the American Association of Anatomists·B D Abbott, M R Probst
Nov 1, 1984·Archives of Environmental Contamination and Toxicology·J E HoseM L Landolt
Jun 15, 1987·Biochemical Pharmacology·G H LambertA N Kotake
Jan 1, 1980·Pharmacology & Therapeutics·O Pelkonen
Jan 1, 1983·Pharmacology & Therapeutics·J V Aranda, L Stern
Apr 1, 1995·International Journal of Immunopharmacology·Z L Lummus, G Henningsen
Mar 1, 1988·Toxicology Letters·J Anwer, N K Mehrotra
Jan 1, 1989·Reproductive Toxicology·Richard H FinnellS M Taylor
Jun 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·S M GallowayR A Pedersen
Nov 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·R Filler, K J Lew
May 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·R A PedersenS M Galloway
Sep 1, 1979·Journal of Toxicology and Environmental Health·D J Hoffman
Oct 1, 1985·European Journal of Biochemistry·R O JuvonenM A Lang
Jan 1, 1982·European Journal of Clinical Pharmacology·J M LanaoF Nuño
Jan 1, 1993·Critical Reviews in Toxicology·R E PetersonG L Kimmel
Jan 1, 1994·Critical Reviews in Toxicology·M Pasanen, O Pelkonen
Jan 1, 1989·Critical Reviews in Toxicology·D W Nebert
Jun 3, 2015·Birth Defects Research. Part A, Clinical and Molecular Teratology·Jacqueline L O'BrienNational Birth Defects Prevention Study
Aug 1, 1980·Teratology·G F Chernoff
Nov 1, 1984·American Journal of Medical Genetics·Richard H Finnell, G F Chernoff
Dec 6, 1997·Biochemical and Biophysical Research Communications·I J LeeB J Song
Nov 8, 2008·The Journal of Pediatrics·Gary M ShawPer M Ueland
Mar 1, 1996·Clinical Pharmacology and Therapeutics·C P DenaroN L Benowitz


Jan 1, 1977·Advances in Cancer Research·S S Thorgeirsson, D W Nebert
May 1, 1977·Biochemical Pharmacology·D R Mattison, S S Thorgeirsson
Apr 1, 1975·Journal of Cellular Physiology·D W NebertA P Poland
Jan 1, 1975·Annual Review of Biochemistry·C Heidelberger
May 15, 1974·International Journal of Cancer. Journal International Du Cancer·R E KouriC E Whitmire
Jan 1, 1966·Biochemical Pharmacology·P J Creaven, D V Parke
Sep 1, 1973·Environmental Health Perspectives·B A SchwetzC G Gerbig
Jan 1, 1971·Proceedings of the National Academy of Sciences of the United States of America·B B BrodieJ R Gillette
Jan 1, 1974·Advances in Cancer Research·P Sims, P L Grover
Aug 16, 1974·Science·D M Jerina, J W Daly
Nov 1, 1971·Toxicology and Applied Pharmacology·K D Courtney, J A Moore
Feb 15, 1968·Life Sciences. Pt. 2: Biochemistry, General and Molecular Biology·R KuntzmanA H Conney
Nov 1, 1961·Journal of Reproduction and Fertility·L D SAVKURB N SRIDHARAN

Related Concepts

Metabolic Process, Cellular
Chemical Burns
Aplastic Anemia
C57BL/6N Mouse
Enzymes, antithrombotic
Congenital Neurologic Anomalies

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