Cyclophosphamide induced DNA strand breaks in mouse embryo cephalic tissue in vivo.
Pregnant C3H mice were exposed to teratogenic doses of cyclophosphamide (CPA), on the 11th day after copulation. The effects of this agent on embryonal cephalic DNA strand breaks were assessed between 3 and 40 h after drug administration. Administration of 15, 30 and 60 mg CPA/kg body weight resulted in conversion of 23, 30 and 44% of the DNA to the single-stranded form, respectively. No detectable DNA damage was evident 3 h after drug administration, but after 6 h significant DNA damage had occurred, reaching a maximum after 9 h. However, no evidence of DNA strand breaks was present at 22, 30 and 40 h after CPA treatment, suggesting that these lesions had been repaired. These findings demonstrate that cephalic DNA damage induced by CPA in the developing mouse embryo occurs in a time and concentration dependent manner, and provide some insight into the kinetics of formation and removal of DNA strand breaks caused by CPA in vivo.
Pillans
P I
PI
Department of Pharmacology, University of Cape Town Medical School, South Africa.
Ponzi
S F
SF
Parker
M I
MI
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000818:Animals; D001921:Brain / Q000002:abnormalities / Q000187:drug effects / Q000196:embryology*; D003520:Cyclophosphamide / Q000633:toxicity*; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D051379:Mice; D008809:Mice, Inbred C3H; D011247:Pregnancy; D013997:Time Factors
D003520:Cyclophosphamide; D004247:DNA