MYELOSUPPRESSIVE ACTIVITY OF 2 HERBICIDES, ATRAZINE AND DINOTERB, ON HUMAN HEMATOPOIETIC PROGENITOR CELLS - AN IN-VITRO ASSAY TO EVALUATE THE EFFECTS OF INTERMEDIATE OR LONG-TERM EXPOSURE

The effects of chronic exposure to phytosanitary products are difficul t to determine because of their use in combination with other products and their variety of formulations containing additives or contaminant s. In order to evaluate, at the cellular level, the risk of myelosuppr essive effects caused by two widely used herbicides, atrazine and dino terb, we performed in vitro assays on human granulomonocytic progenito r-cells (CFU-GM) and also granulomonocytic expansion in liquid media. Both of these techniques were carried out in the presence of each mole cule. Seven stable environmental metabolites of atrazine were studied using the above techniques in addition to supernatants of rat hepatocy tes preincubated with atrazine and dinoterb for 24 hr. Parent atrazine and dinoterb showed similar moderate direct toxicity on CFU-GM. In ce lls grown in liquid media for a period longer than 14 days, dinoterb t oxicity appeared delayed but increased when compared with atrazine. 2- chloro-diamino-atrazine was found to be as toxic as atrazine on CFU-GM . Supernatants of rat hepatocyte preincubated for 24 hr with dinoterb exhibited a 150-fold increase in toxicity compared with the parent mol ecule, while toxicity remained unchanged for atrazine. This phenomenon was directly correlated to toxicity on rat hepatocytes. The present s tudy will be useful in defining tissue-specific toxicities of phytosan itary products, including environmental or biotransformed metabolites. (C) 1998 Elsevier Science Ltd. All rights reserved.