A teratologic suppressor role for p53 in benzo[a]pyrene-treated transgenic p53-deficient mice

Nat Genet. 1995 Jun;10(2):181-7. doi: 10.1038/ng0695-181.


DNA damage may mediate birth defects caused by many drugs and environmental chemicals, therefore p53, a tumour suppressor gene that facilitates DNA repair, may be critically embryoprotective. We have studied the effects of the environmental teratogen, benzo[a]pyrene, on pregnant heterozygous p53-deficient mice. Such mice exhibited between 2- to 4-fold higher embryotoxicity and teratogenicity than normal p53-controls. Fetal resorptions reflecting in utero death were genotyped using the polymerase chain reaction and found to be increased 2.6-fold and 3.6-fold respectively with heterozygous and homozygous p53-deficient embryos. These results provide the first direct evidence that p53 may be an important teratological suppressor gene which protects the embryo from DNA-damaging chemicals and developmental oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Drug-Induced / genetics*
  • Animals
  • Base Sequence
  • Benzo(a)pyrene / pharmacology*
  • Cytochrome P-450 Enzyme System / drug effects
  • Enzyme Induction
  • Female
  • Fetal Resorption / genetics
  • Gene Deletion
  • Genes, p53*
  • Genotype
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Biological
  • Molecular Sequence Data
  • Polychlorinated Dibenzodioxins / pharmacology
  • Pregnancy
  • Pregnancy, Animal / drug effects*
  • Pregnancy, Animal / genetics


  • Polychlorinated Dibenzodioxins
  • Benzo(a)pyrene
  • Cytochrome P-450 Enzyme System