A teratologic suppressor role for p53 in benzo(a)pyrene–treated transgenic p53-deficient mice

Abstract

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.