Mutagenic and teratogenic effects of cyclophosphamide on the chick embryo: chromosomal aberrations and cell proliferation in affected and unaffected tissues.
Chromosomal aberrations and cell proliferation were analyzed in the chick embryo blood, limb bud, and facial tissues 12 and 24 hours after cyclophosphamide (CP) administration on day 3. The cytogenic findings were compared with teratogenic effects evaluated on incubation day 8. Low dose (0.3 micrograms) resulting in heart defects exclusively, increased the frequency of aberrant cells with simultaneous depression of cell proliferation in blood only. High dose of CP (6 micrograms), besides the heart defects, also induced facial clefts and limb malformations, and strong clastogenic effects associated with mitotic inhibition were observed in all tissues investigated. The results support the idea that the consequences of mutagenic action of cyclophosphamide--cell cycle delay and excessive death of cells with unstable aberrations--result in abnormal morphogenesis.
Novotná
B
B
Institute of Experimental Medicine, Czechoslovak Academy of Sciences, Prague, Czechoslovakia.
Jelínek
R
R
D000818:Animals; D002642:Chick Embryo; D002645:Chickens; D002869:Chromosome Aberrations; D003520:Cyclophosphamide / Q000633:toxicity*; D004912:Erythrocytes / Q000187:drug effects; D005145:Face / Q000002:abnormalities; D006330:Heart Defects, Congenital / Q000139:chemically induced; D017880:Limb Deformities, Congenital; D008938:Mitosis / Q000187:drug effects; D009024:Morphogenesis; D009153:Mutagens; D013723:Teratogens
D009153:Mutagens; D013723:Teratogens; D003520:Cyclophosphamide