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NIEHS Joins EPA and NCI in Agricultural Health Study

Environmental Health Perspectives
Environmental Health Perspectives
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  • Environews: Niehs News
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e~~~~~~~~~ York), who introduced "DES Education and Research Amendments of 1992" (H.R. 4178); the companion bill was S.2837, introduced by Senator Tom Harkin (D- Iowa). Role of p53 in Cellular Response to DNA Damage Normally, when DNA is damaged, synthe- sis of new DNA is halted until the DNA is repaired. If synthesis is not halted, newly synthesized DNA may be at risk for genet- ic errors, which could lead to malignancies. Michael Kastan, an NIEHS grantee at Johns Hopkins University, has investigated the role of p53 in the cellular response to DNA damage. Elucidation of p53 gene expression is particularly important be- cause it is the most commonly mutated gene in human cancer. Kastan's laboratory has demonstrated, confirmed, and clarified the link between p53 and the arrest of the cell cycle at the GI phase after ionizing radiation. His lab- oratory has observed this phenomenon in many cell types and in several tumor cell lines. Kastan and colleagues transfected a cell line (HL-60) that had no endogenous p53 with wild-type p53. These transfected cells demonstrated GI arrest after irradia- tion. A tumor cell line was transfected with a mutant p53 gene and did not dem- onstrate GI arrest after irradiation. Normal fibroblasts from mice in which both alleles of p53 had been disrupted were defective at this GI checkpoint. Kastan's laboratory is now investigating agents that affect p53 levels. Topoisom- erase inhibitors induce p53, whereas base- damaging agents do not. Kastan is also studying the biochemical pathways involved in altering p53 protein levels and cell-cycle progression after DNA damage. His group has demonstrated that genes that are defective in the cancer-prone dis- ease ataxia-telangiectasia are necessary for the induction of the p53 protein. Finally, they have shown that the gene GADD45, which is activated by growth arrest or DNA damage, is regulated by p53. Air Pollutant Related to Genetic Damage in Poland Frederica Perera and colleagues at Colum- bia University, Sweden's Center fo

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