THE EFFECT OF HEPTACHLOR, A CHLORINATED-HYDROCARBON INSECTICIDE ON P53 TUMOR-SUPPRESSOR IN HUMAN-LYMPHOCYTES

Previous studies have shown that heptachlor, a chlorinated hydrocarbon insecticide, is a liver tumor promoter in rats and mice and induces t umor promoting-like alterations in human myeloblastic leukemia cells. The nature of tumor promotion is multifaceted and has recently been sh own to include suppression of programmed cell death (apoptosis) as a m echanism by which a tumor promoter can prolong cell viability. The abi lity of tumor promoters to suppress apoptosis prompted us to address t he question of whether heptachlor is capable of effecting the expressi on of genes involved in lymphocyte apoptosis, in particular, the p53 t umor suppressor gene. Experiments with a CEM x 174 cell line, a hybrid of human T and B cells, revealed that heptachlor downregulated p53 ge ne expression at the post-transcriptional level without changing level s of mRNA in the cells. The heptachlor-induced reduction in the basal levels of expression of this gene was both in a concentration and time -dependent manner. (C) 1998 Elsevier Science Ireland Ltd. All rights r eserved.