Abstracts, NIEHS Second Biennial Science Seminar

Clinical observations have strongly implicated a number of antiseizure agents as human teratogens. The embryopathic potential of three classes of anticonvulsants: oxazolidinediones (OX); hydantoins (Hy), and succinimides (Su) have been evaluated in our laboratory using the CD-1 mouse. Estimated adult lethality curves were used as the basis for selecting doses for teratogenic investigation. Several dose levels were evaluated and no observable maternal toxicity was noted. Following treatment on days 8-10 of pregnancy increased incidence of congenital abnormalities in the skeletal and cardiovascular systems of the offspring were observed. The dose in mmole/kg/day which produced a 5% incidence and constitutes a significant (p s 0.01) increase in malformations was estimated and used to determine the relative teratogenic potentials of these compounds. With trimethadione and paramethadione (OX) the values were 0.54 and 1.07, respectively. Phenytoin and ethotoin (Hy) gave values of 0.16 and 1.97, respectively, while the values for ethosuximide, methsuximide, and phensuximide (Su) were 4.91, 1.58, and 2.25, respectively. These values were well below the adult LDol. On comparing the relative teratogenicity of each anticonvulsant with respect to their relative risk to the dam and expressed as a function of the adult LD5o, it was found that the teratogenicity of oxazolidinediones was significantly greater than that of the hy-dantoins and succinimides. These compounds share a common chemical nucleus, suggesting the possibility of a structure-teratogenic activity relationship which is being further explored. The major secretory product of the rat ventral prostate is a glycoprotein of molecular weight 51,000. This protein is under direct androgen control. Under reduced-denaturing condition this protein migrates as three polypeptides of molecular weights of 14,000, 11,000, and 8,000 daltons. The major protein is glycopro-tein of 14,000 daltons. Approximately 45% of the total poly (A+)-RNA from rat ventral prostate migrates as a single peak at lOS during sucrose density gradient centrifugation. This 10S poly (A+)-mRNA produces three polypeptides of molecular weight 13,000, 10,000 and 9,000 daltons in the heterologous wheat germ translation system. When this lOS poly(A+)-mRNA is analyzed by denaturing (methylmercury hydroxide) agar gel electrophoresis, two major bands of RNA are observed at sizes of 600 NT and 500 NT. The larger RNA of 600 NT is in approximately twice the concentration as the 500 NT mRNA. By fractionation of the lOS mRNApMS,, it was shown that the light side of the lOS (500 NT band) peak produces the 13,000 MW polypeptide in the wheat germ system, while …