RETINOIC ACID-INDUCED STRESS PROTEIN-SYNTHESIS IN THE MOUSE

We have previously demonstrated that stress proteins (SPs) are synthes ized in tissues in which malformations are later observed following tr eatment with the developmental toxicant, retinoic acid (RA), on day 11 of gestation (GD 11). These proteins were not synthesized in tissues which did not present with malformations near partuition. The purpose of the present investigation was to determine if this correlation betw een early SP synthesis and later malformation was present at other tim es during gestation. CD-1 strain mice were dosed orally with corn oil or 100 mg/kg body weight RA on GD 10 or 13. Some of the mice in each g roup were given an intraperitoneal injection of H-3-leucine to label e mbryonic protein synthesis one hour after dosing with RA. These animal s were sacrificed 1.5 hour later, and embryonic protein synthesis was determined by two-dimensional gel electrophoresis followed by autoradi ography. Other animals in each group were sacrificed on day 17 of gest ation, and fetuses were examined for the presence of malformations. Fo llowing treatment with RA on day 10 of gestation, malformations were o bserved in the forelimbs, the hindlimbs and the tail; heart defects we re not observed. SPs of 20-25,000 and 90,000 relative molecular mass ( Mr) were synthesized in the forelimb bud and tail; in addition, a seco nd low molecular weight (20-25,000) and a 84,000 Mr SPs were synthesiz ed in forelimb buds. No SPs were synthesized in the hindlimb bud or th e heart. Following RA treatment on GD 13, cleft palate was observed in 58% of fetuses; no other malformations were found. Proteins of 34,000 , 84,000 and 90,000 Mr were synthesized in craniofacial tissue; SPs we re not observed in forelimb bud, hindlimb bud, heart or tail tissues a t this time. Therefore, it appears that there may be a correlation bet ween tissue-specific SP synthesis early in organogenesis and the prese nce of a malformation later in gestation.