Incorporation of 5-lododeoxyuridine into the DNA of mouse embryos: its relation to embryotoxicity.
Pregnant female ICR mice were administered, ip, either a trace (200 muCi/kg) or teratogenic (200 muCi + 300 mg/kg) dose of [6(-3)H] 5-iododeoxyuridine (IdU) on day 10 of gestation. Maternal liver, spleen, intestine, and kidneys, and placentas and embryos were removed at various time intervals after injection, weighed, and homogenized in cold 0.5 m perchloric acid. The half-lives of IdU-derived nucleotides in the acid-soluble fraction ranged from 31-46 min (trace) to 57-131 min (teratogenic) for the tissues analyzed. [3H]IdU was incorporated into the DNA of all mitotically active tissues after both dosages. The presence of the label in iodouracil was demonstrated by thin-layer chromatography of DNA bases extracted from maternal spleen and embryo. Growth of embryos following injection on day 10 resulted in decreased 3H-specific activity in the DNA fraction and concomitant retention of total activity. It is suggested that the previously demonstrated embryotoxicity of IdU is related to its retention at its presumed intracellular site of action.
D000818:Animals; D001973:Bromodeoxyuridine / Q000009:adverse effects / Q000378:metabolism; D002855:Chromatography, Thin Layer; D004247:DNA / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D007065:Idoxuridine / Q000009:adverse effects* / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008813:Mice, Inbred ICR; D009929:Organ Size; D010920:Placenta / Q000473:pathology; D011247:Pregnancy; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D013723:Teratogens / Q000378:metabolism
D013723:Teratogens; D004247:DNA; D001973:Bromodeoxyuridine; D007065:Idoxuridine