ESTROGENIC XENOBIOTICS AFFECT THE INTRACELLULAR ACTIVATION SIGNAL IN MITOGEN-INDUCED HUMAN PERIPHERAL-BLOOD LYMPHOCYTES - IMMUNOTOXICOLOGICAL IMPACT

The present study was an attempt to elucidate the effect of estrogenic xenobiotics on the proliferation of mitogen-stimulated human peripher al blood lymphocyte (PBL). Our findings follow : (a) the proliferation of PBL in response to phytohemagglutinin (PHA) was mediated by protei n kinase C activity, but estrogenic xenobiotics had a strong inhibitor y effect on protein kinase C activity of PHA-stimulated PBL; (b) cytop lasmic extracts from PHA-stimulated PBL greatly activated DNA replicat ion, but estrogenic xenobiotics had a strong inhibitory effect on thes e activities. The results suggest that the cytoplasmic signal-generati ng system in mitogen-treated PBL is inhibited by estrogenic xenobiotic s, and that the defect occurs at all stages in the sequence of events leading to DNA synthesis and cell proliferation. (C) 1998 Internationa l Society for Immunopharmacology. Published by Elsevier Science Ltd.