The contractor's objective is to investigate the carcinogenic and mutagenic effects of four compounds, 5-azacytidine, hydroxyurea, cytosine arabinoside, and deoxyazacytidine, in two in vivo systems. First, the contractor will assess the ability of the four drugs to induce chromosomal aberrations in the bone marrow cells of male rats. Next, the maximum tolerated doses of these compounds, excluding 5-azacytidine which already has an established maximum tolerated dose, will be determined in male and female rats and mice using a 14 day study. The above mentioned compounds induce the production of fetal hemoglobin when administered to either baboons or to human patients with beta thalassemia or sickle cell anemia. Since this therapy may become more widely used, it is important to determine which of these drugs has no long-term risk.
