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Comparative analysis of HPRT mutant frequency in children with cancer
Author(s) -
Rice Sederick C.,
Vacek Pamela M.,
Homans Alan H.,
Kendall Heather,
Rivers Jami,
Messier Terri,
Finette Barry A.
Publication year - 2003
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.10171
Subject(s) - hypoxanthine guanine phosphoribosyltransferase , somatic cell , cancer , neuroblastoma , leukemia , cancer research , lymphoma , pediatric cancer , genome instability , medicine , mutation frequency , carcinogenesis , mutation , biology , mutant , oncology , gene , genetics , immunology , dna damage , dna , cell culture
The link between exposure to environmental mutagens and the development of cancer is well established. Yet there is a paucity of data on the relationship between gene–environment interactions and the mechanisms associated with the somatic mutational events involved with malignant transformation, especially in children. To gain insight into somatic mutational mechanisms in children who develop cancer, we determined the background mutant frequency (Mf) in the hypoxanthine phosphoribosyl transferase ( HPRT ) reporter gene of peripheral blood lymphocytes from pediatric cancer patients at the time of diagnosis and prior to therapeutic intervention. We studied 23 children with hematologic malignancies and 31 children with solid tumors prior to initial therapeutic intervention. Children with solid tumors, specifically sarcomas, and Hodgkin's disease were significantly older and had elevated HPRT Mfs (6.1 × 10 −6 and 3.7 × 10 −6 , respectively) at the time of diagnosis, compared to normal controls (2.3 × 10 −6 ) and other pediatric tumor groups including children with acute lymphocytic leukemia and non‐Hodgkin's lymphoma (ALL/NHL, 1.7 × 10 −6 ), central nervous system tumors (CNS, 3.6 × 10 −6 ), and neuroblastoma (1.9 × 10 −6 ). Of importance is that the significant differences observed in HPRT Mfs between these groups no longer existed after correcting for the effects of age. These data demonstrate that in children who develop cancer there appears to be no significant increase in background HPRT Mf that would indicate significant exposure to genotoxic chemicals or an underlying DNA repair defect resulting in genomic instability. In addition, these data demonstrate the importance of correcting for the effect of age when comparing the frequency of somatic mutations in children and should provide baseline data for future longitudinal biomonitoring studies on the genetic effects of chemotherapy in children treated for cancer. Environ. Mol. Mutagen. 42:44–49, 2003. © 2003 Wiley‐Liss, Inc.