A TERATOLOGIC SUPPRESSOR ROLE FOR P53 IN BENZO[A]PYRENE-TREATED TRANSGENIC P53-DEFICIENT MICE

DNA damage may mediate birth defects caused by many drugs and environm ental chemicals, therefore p53, a tumour suppressor gene that facilita tes DNA repair, may be critically embryoprotective. We have studied th e effects of the environmental teratogen, benzo[a]pyrene, on pregnant heterozygous p53-deficient mice. Such mice exhibited between 2- to 4-f old 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-f old respectively with heterozygous and homozygous p53-deficient embryo s. 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.