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The somatic mutant frequency (Mf) of the hypoxanthine phosphoribosyl transferase (HPRT) gene has been widely used as a biomarker for the genotoxic effects of exposure but few studies have found an association with environmental exposures. We measured background Mfs in 49 current and former residents of Dover Township, New Jersey, who were exposed during childhood to industrially contaminated drinking water. The exposed subjects were the siblings of children who developed cancer after residing in Dover Township, where the incidence of childhood cancer has been elevated since 1979. Mfs from this exposed group were compared to Mfs in 43 age‐matched, presumably unexposed residents of neighboring communities with no known water contamination and no increased cancer incidence. Statistical comparisons were based on the natural logarithm of Mf (lnMF). The mean Mf for the exposed group did not differ significantly from the unexposed group (3.90 × 10−6vs. 5.06 × 10−6; P= 0.135), but unselected cloning efficiencies were higher in the exposed group (0.55 vs. 0.45; P= 0.005). After adjustment for cloning efficiency, lnMf values were very similar in both groups and age‐related increases were comparable to those previously observed in healthy children. The results suggest that HPRTMf may not be a sensitive biomarker for the genotoxic effects of environmental exposures in children, particularly when substantial time has elapsed since exposure. Environ. Mol. Mutagen., 2005. © 2005 Wiley‐Liss, Inc.

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 HPRTMfs (6.1 × 10−6and 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 HPRTMfs 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 HPRTMf 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.

No abstract.