The effect of heptachlor, a chlorinated hydrocarbon insecticide, on p53 tumor suppressor in human lymphocytes

Studies have shown that heptachlor, a chlorinated hydrocarbon insecticide used in the control of termites and fire ants, is a liver tumor promoter in rats and mice and induces tumor promoting-like alterations in human myeloblastic leukemia cells. The nature of tumor promotion is multifaceted and has recently been shown to include suppression of programmed cell death (apoptosis) as a mechanism by which a tumor promoter can prolong cell viability. The ability of tumor promoters to suppress apoptosis prompted us to address the question of whether heptachlor is capable of effecting the expression of genes involved in lymphocyte apoptosis, in particular, the p53 tumor suppressor gene. Treatment of the CEM X174 cell line, a hybrid of human T and B cells, revealed that heptachlor down-regulated p53 gene expression at the post-transcriptional level without changing levels 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. The downregulation of p53 tumor suppressor protein levels may represent another mechanism by which tumor promotion can occur in lymphocytes.