FREE-RADICAL TERATOGENICITY IN PHENYTOIN-TREATED MICE

Objective: The purpose of this study was to test the hypothesis that phenytoin-induced fetal cleft palate formation in mice is associated with enhanced free radical interactions. Methods: The extent of free radical interactions was estimated by measuring lipid peroxidation capacity. Malondialdehyde, a by-product of lipid peroxidation, was used to measure lipid peroxidation in fetal tissues of pregnant, phenytoin-treated mice. Group I consisted of 13 pups from 2 phenytoin-treated maternal mice (dams) and 10 pups from 2 control dams. Individual fetal heads were obtained on day 19 of gestation (1 day before spontaneous birth). Group II consisted of 80 pups from 8 phenytoin-treated dams and 70 pups from 7 controls. Mice were sacrificed and fetal heads from each dam were pooled on day 13 because on days 12 and 13 the murine palate is formed. Results: The incidence of cleft palate was greater in the pups of the phenytoin-treated dams than in the control group (69.2% vs 0%). Malondialdehyde concentration (nmol/100 mg protein) in group I was 301.1 +/- 32.2 for controls and 285.9 +/- 27.4 for the phenytoin-treated dams (P = 0.71). Malondialdehyde concentration in group II was 197.7 +/- 13.7 for controls and 257.0 +/- 33.0 for phenytoin-treated dams (P = 0.3). Conclusion: Our results show that phenytoin-induced fetal cleft palate formation is associated with unchanged lipid peroxidation at the time of fetal palate formation (day 13) and one day prior to delivery (day 19). These data suggest that free radical injury is either not involved in teratogenic effects of phenytoin, or that it is at a level that cannot be detected using these techniques.