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 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.
Nicol
C J
CJ
Dept. of Pharmacology, University of Toronto, Ontario, Canada.
Harrison
M L
ML
Laposa
R R
RR
Gimelshtein
I L
IL
Wells
P G
PG
D000014:Abnormalities, Drug-Induced / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D004790:Enzyme Induction; D005260:Female; D005327:Fetal Resorption / Q000235:genetics; D017353:Gene Deletion; D016158:Genes, p53; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D008969:Molecular Sequence Data; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects* / Q000235:genetics
D000072317:Polychlorinated Dibenzodioxins; D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System