The primary focus of work in the Molecular Genetics Section continues to be on growth regulation in mammalian cells. The investigation of growth inhibitory activity detected by DNA- mediated gene transfer is emphasized within this framework. Over the past year two techniques, magnetic affinity cell sorting (MACS) and fluorescence activated cell sorting (FACS) have been used in conjunction with gene transfer to measure transient growth regulation mediated by exogenous DNA sequences. Several results of interest have been obtained: i) at the polypeptide level, development of an efficient transfection protocol for human embryo fibroblasts has led to initiation of a project in which cDNA libraries are screened for genes involved in senescence and tumor suppression, ii) at the RNA level, evidence has been obtained for growth regulation, both positive and negative, by RNA polymerase III-encoded transcripts; mutational studies to derive structure/function relationships for 7SL RNA- and Alu-mediated growth control are in progress, iii) at the DNA level, cytotoxicity has been found to follow introduction of retroviral, e.g., HIV, long terminal repeat sequences; this finding may have implications for mechanisms of viral pathogenicity.
