Effect of the chlorinated hydrocarbons heptachlor, chlordane, and toxaphene on retinoblastoma tumor suppressor in human lymphocytes

Organochlorine use over the past 50 years has resulted in the contamination of soil, water, plant and animal species. This contamination has created a long-lasting environmental problem, as the members of the organochlorine c lass of pesticides are resistant to degradation and have been labeled as pe rsistent bioaccumulators. Studies have shown certain organochlorines to be tumor promoters, liver toxicants and to induce immune cell dysfunction in r ats and mice. Our laboratory has shown that the organochlorines heptachlor and chlordane affect leukocytic gene expression and differentiation. In thi s study, experiments with CEM x 174 cells, a hybrid of human T and B cells, were performed to investigate the effects of the tumor promoter heptachlor and its congeners chlordane and toxaphene on retinoblastoma (Rb) gene expr ession. The results indicated that heptachlor, chlordane or toxaphene, in t he range of 10-50 mu M, were able to reduce Rb protein levels in a concentr ation-dependent manner. In the case of heptachlor, the reduction could be s een as early as 12 h and was time-dependent. Analysis of Rb mRNA levels rev ealed no detectable difference over the same concentration range. These res ults suggest that members of the organochlorine class are able to downregul ate Rb expression at the post-transcriptional level, an effect similar to t hat on p53 tumor suppressor previously reported by our laboratory. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.