Prospective study of mutant frequencies at the hprt and T-cell receptor gene loci in pediatric cancer patients during chemotherapy.
Mutant frequencies (MFs) at the hypoxanthine phosphoribosyl transferase gene and the T-cell receptor (TCR) gene loci were evaluated in nine pediatric cancer patients before and during anticancer chemotherapy. The study population consisted of three patients with Hodgkin's disease, four patients with neuroblastoma, and two patients with Wilms' tumor. Except for one patient with neuroblastoma and one patient with Wilms' tumor, MFs at the hypoxanthine phosphoribosyl transferase locus tended to increase during the early cycles of treatment. The elevation was most striking and persistent in patients with Hodgkin's disease. The clonal relationship was determined in mutant cells derived from Hodgkin's disease patients by TCR-gamma gene rearrangement pattern and showed that the elevation of MFs resulted from increased mutational events rather than from clonal expansion of mutants. An increase in TCR MF was also found during chemotherapy in most patients, but the time of TCR MF elevation was variable among patients. Among the chemotherapeutic agents used in this study, cyclophosphamide was considered to be the most mutagenic. Our present study clearly demonstrates that anticancer chemotherapy can induce mutagenesis in vivo in various pediatric cancer patients.
Department of Pediatrics, Kyoto University, Japan.
M
M
Sawada
M
M
Kubota
Y W
YW
Lin
K
K
Watanabe
S
S
Koishi
I
I
Usami
Y
Y
Akiyama
T
T
Matsumura
K
K
Furusho
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D016001:Confidence Intervals; D003520:Cyclophosphamide / Q000008:administration & dosage; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000187:drug effects*; D006689:Hodgkin Disease / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000187:drug effects / Q000235:genetics*; D007223:Infant; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000187:drug effects*; D009447:Neuroblastoma / Q000188:drug therapy / Q000235:genetics*; D011446:Prospective Studies; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000235:genetics*; D009396:Wilms Tumor / Q000188:drug therapy / Q000235:genetics*
D011948:Receptors, Antigen, T-Cell; D003520:Cyclophosphamide; D007041:Hypoxanthine Phosphoribosyltransferase