INDUCTION OF A HEAT-SHOCK RESPONSE (HSP-72) IN RAT EMBRYOS EXPOSED TOSELECTED CHEMICAL TERATOGENS

A monoclonal antibody to the 72 kD heat shock protein (HSP 72), Wester n blot analysis and 2-D gel electrophoresis/autoradiography were used to determine whether selected chemical teratogens induced the synthesi s and accumulation of HSP 72 in postimplantation rat embryos exposed i n vitro. The chemical teratogens studied include N-Acetoxy-2-acetylami nofluorene (N-Ac-AAF), cadmium chloride (CAD), cyclophosphamide (CP), sodium arsenite (AS), and sodium salicylate (SAI). Exposures to test c hemicals were selected that produced obvious embryotoxicity characteri zed by abnormal development and growth retardation. Of the five chemic al teratogens studied, AS and SAI induced the synthesis and accumulati on of HSP 72 in day 10 rat embryos. The kinetics of HSP 72 accumulatio n, however, differed between AS- and SAL-treated embryos. Maximal leve ls of HSP 72 were observed 24 hours after AS exposure and 10 hours aft er SAI exposure. N-Ac-AAF, CD, and CP induced obvious embryotoxicity; however, none of these chemical teratogens induced HSP 72 at any of th e timepoints assayed. Although only a small sample of chemical teratog ens was studied, our results suggest that the heat shock response, cha racterized by the synthesis and accumulation of HSP 72, is not a gener al biomarker for chemical teratogens. (C) 1994 Wiley-Liss, Inc.