ABSTRACT Glutathione (GSH) is a tripeptide consisting of cysteine, glutamic acid and glycine, and plays an important role in detoxification reactions. In this report, we describe (1) the effects of the depleting agents of GSH such as diethylmaleate (DEM), phorone, and buthionine sulfoximine (BSO) on teratogenicity of 5-fluorouracil (5-FU) in mice, (2) the effects of GSH or N-acetyl-L-cysteine (NAC), a precursor of GSH on teratogenicity of 5-FU or cadmium hydrochloride (Cd) in mice. Pregnant ICR mice were injected intra- peritoneally (i.p.) with 5-FU at dose levels of 20, 25, and 30 mg/kg on day 11 of gestation (vaginal plug = day 0). Mice were injected i.p. with DEM, phorone, or BSO 4 to 6 hours before dosing with 5-FU. Mice were also pretreated intravenously (i.v.) with GSH at dose levels of 150, 300 and 600 mg/kg, or NAC at dose levels of 80, 160, and 320 mg/kg 0.5 to 2 hours before dosing with 5-FU. In the Cd-teratogenicity study, mice were injected i.v. with GSH or NAC before dosing with Cd at 3.5 mg/kg i.p. on day 11 of gestation. Pretreatment with DEM, phorone or BSO increased the incidence of oligodactyly induced by 5-FU, while pretreatment with GSH or NAC decreased the incidences. Pretreatment with GSH or NAC decreased the incidence of cleft palate and abnormal palatal rugae induced by Cd. The results suggest that cysteine plays a key role in the teratogenicity of 5-FU or Cd in mice.
ABSTRACT The diagnostic efficacy was compared between the fluorescent CA repeat polymorphism analysis and polymerase chain reaction-restriction fragment length poly- morphism (PCR-RFLP) analysis for carrier diagnosis of Duchenne muscular dystrophy. Nine females from seven pedigrees were examined. Polymorphic alleles were examined by the fluorescent labelling method in eight loci within the dystrophin gene. PCR-RFLP analysis was performed in a total of six loci within the dystrophin gene. Carrier diagnosis could not be made in three females of two pedigrees due to an inability to detect polymorphic alleles by PCR-RFLP. In contrast, CA repeat polymorphism analysis allowed successful carrier diagnosis in nine subjects. These findings suggest that the fluorescent CA repeat polymorphism analysis provides a simple, safe and effective alternative to PCR- RFLP analysis for carrier diagnosis of Duchenne muscular dystrophy. Key words: CA repeat polymorphism, carrier diagnosis, Duchenne muscular dystrophy.