[Induction of fragile sites by chemical and physical agents]

Many human malignancies are thought to be caused in large part by environmental agents. Studies indicate that ionizing radiation and many chemical mutagens/carcinogens appear to induce chromosomal mutations. Recently, it was suggested that chromosome aberrations (CA) might be produced by breakage at specific chromosomal points known as fragile sites (FS). FS induced by different chemical agents has been widely analyzed in lymphocytes cultures, but very little is known of the environmental factors that may influence on FS expression. No studies exist about FS expression induced with X-rays or about the interaction between radiation and chemical FS inducers. In this work FS expression induced by X-rays and 3 known FS inducers such as: BUDR, FUDR and aphidicolin, is analyzed. It was found that 17 chromosomal bands were significantly damaged (p < 0.001), thus being defined as FS. FS 3p14 and 16q23 were the more frequently observed. CA and FS levels from cultures exposed to X-rays and to FUDR plus X-rays were significantly increased (p < 0.01), suggesting that it would be convenient to use other radiosensitizer. These results suggest that FS could be induced by environmental factors such as chemical or physical agents. Finally, the correlation between FS and radiation induced CA, cancer CA and oncogene localization was established, showing the importance of the interaction between FS, CA and oncogenes in cancer development.