Cancer chemotherapy and somatic cell mutation

The occurrence of a second neoplasm is one of the major obstacles in cancer chemotherapy. The elucidation of the genotoxic effects induced by anti-can cer drugs is considered to be helpful in identifying the degree of cancer r isk. Numerous investigations on cancer patients after chemotherapy have dem onstrated: (i) an increase in the in vivo somatic cell mutant frequency (Mf ) at three genetic loci, including hypoxanthine-guanine phosphoribosyl-tran sferase (hprt), glycophorin A (GPA), and the T-cell receptor (TCR), and (ii ) alterations in the mutational spectra of hprt mutants. However, the time required for and the degree of such changes are quite variable among patien ts even if they have received the same chemotherapy, suggesting the existen ce of underlying genetic factor(s). Accordingly, some cancer patients prior to chemotherapy as well as patients with cancer-prone syndrome have been f ound to show an elevated Mf. Based on the information obtained from somatic cell mutation assays, an individualized chemotherapy should be considered in order to minimize the risk of a second neoplasm. (C) 2000 Elsevier Scien ce B.V. All rights reserved.