FREQUENCIES OF HPRT MUTANTS AND MICRONUCLEI IN LYMPHOCYTES OF CANCER-PATIENTS UNDER CHEMOTHERAPY - A PROSPECTIVE-STUDY

Fifteen cancer patients, including 10 testicular carcinoma patients, w ere treated with several types of combination chemotherapy. Blood samp les were collected before, during and after chemotherapy. Subsequently , lymphocytes were analyzed for frequencies of HPRT mutants (MF) and m icronuclei (MNF). Significantly elevated MFs were detected in eight pa tients. Mean expression time (+/- SD) for mutations was 98 +/- 54 days (range: 42-172 days). In some patients, enhanced MFs persisted for a period of 430-490 days after cessation of chemotherapy. In five patien ts MNFs were increased 2-6-fold and the enhancement was fairly persist ent. Ifosfamide and cyclophosphamide appeared to be the most mutagenic and clastogenic constituents of the chemotherapy, while evidence for adverse effects of adriamycin, 4-epi-adriamycin and bleomycin was equi vocal. Results indicate that the clinical use of mutagenic drugs must be weighed against the risks of persistent genetic damage and secondar y malignancies in cured patients and their potential offspring. Furthe r studies are necessary to determine the true risks and incidence of s uch abnormalities following chemotherapy for curable forms of cancer.