The relationship between the effects of teratogens in vivo and in vitro

Abstract

The effects of the selected agents, insulin, diphenylhydantoin, chloroquine sulphate, chlordiazepoxide HC1, meprobamate, cobaltous chloride and lead nitrate, on the development of chick embryos and on the morphological and biochemical differentiation of cells in culture were investigated. The cultures were established from neural retina, limb and kidney fibroblasts derived from 8-day old chick embryos, and lens epithelium from day -old chicks.In in vivo studies, insulin treatment caused limb, beak, tail and eye defects. Chlordiazepoxide HC1 caused growth retardation, especially of the. limbs. Cobaltous chloride induced lens opacity and thin limbs and lead nitrate caused spinal and brain damage. The incidence and the degree of the defects depended both on the stage of treatment and the amount of the agents administered. In contrast, diphenylhydantoin, chloroquine sulphate and meprobamate did not induce any detectable gross morphological abnormality.In cell culture studies, insulin treatment of cultured lens epithelial and neural retina cells affected both the synthesis and accumulation of several protein components. The effect of insulin on lens epithelial cells was found to vary with the genotype. The effect of insulin on limb fibroblast cell cultures was dependent on the level of FCS in the culture medium. Chlordiazepoxide HC1 treatment of cultured cells affected the synthesis and accumulation of the proteins in neural retina, limb and kidney fibroblast cells. Diphenylhydantoin treatment affected protein synthesis and accumulation in lens epithelial and neural retina 'cell cultures. Chioroquine sulphate treatment affected protein synthesis and accumulation in lens epithelial, neural retina and brain cell cultures. Diphenylhydantoin,chloroquine sulphate and chlordiazepoxide HC1 also affected the activity of choline acetyl transferase in neural retina cell cultures. Lead nitrate was found to affect protein synthesis and accumulation only in neural retina cell cultures. Finally meprobamate affected protein synthesis and accumulation in limb fibroblast cell cultures.The data suggest that certain correlations do exist between in vivo and in vitro teratogenic tests.