This research is based on the hypothesis that deficiency of the nutrient folate is a major contributory factor in the """"""""treatment- related"""""""" or """"""""secondary"""""""" leukemias that develop in patients who have been previously treated with chemotherapy. Most chemotherapeutic agents kill cells by damaging DNA and thus they have the potential to be leukemogenic through their effects on hematopoietic cell DNA. Similarly, folate deficiency impairs the synthesis and repair of DNA such that genetic damage and gene mutation can result. Hematopoietic cells are especially susceptible to both chemotherapy and folate deficiency. Previous studies in patients with untreated or aggressive cancers have shown that these patients are highly likely to develop folate deficiency as their illnesses progress. Studies of folate deficiency in populations with less advanced cancers that have effective chemotherapy and long survivals have not been performed. This study will determine the cumulative incidence of folate deficiency in patients treated with chemotherapy for breast cancer, non-Hodgkin's lymphoma, Hodgkin's disease, and testicular cancer. Serum levels of folate, vitamin B12, and homocysteine and erythrocyte levels of folate will be measured in blood samples taken immediately prior to each cycle of a patient's chemotherapeutic regimen. The levels of uracil misincorporation in DNA will be monitored in blood leukocytes and bone marrow cells. Patients developing either folate or vitamin B12 deficiency will receive supplements of the deficient vitamin. If a high percentage of patient develop folate deficiency, then larger interventional trials of prophylactic folate administration may determine whether this contributary leukemogenic factor can be safely eliminated in these chemotherapy patients and thereby decrease the incidence of secondary leukemias.
