Background-A better knowledge of patient x-ray dose and the associated radiation risk in pediatric interventional cardiology is warranted in view of the extensive use of x-rays and the higher radiosensitivity of children. In the present study, ␥-H2AX foci were used as a biomarker for radiation-induced effects. Patient-specific dose was assessed and radiation risks were estimated according to the linear-no-threshold model, commonly used in radiation protection, and the ␥-H2AX foci data. Methods and Results-In 49 pediatric patients (median age, 0.75 years) with congenital heart disease who underwent cardiac catheterization procedures, blood samples were taken before and shortly after the procedure. ␥-H2AX foci were determined in peripheral blood T lymphocytes. In each patient, a net increase in ␥-H2AX foci, representing DNA double-strand breaks induced by interventional x-rays, was observed. In addition, a patient-specific Monte Carlo simulation of the procedure was performed, resulting in individual blood, organ, and tissue doses. Plotting of ␥-H2AX foci versus blood dose indicated a low-dose hypersensitivity. Median effective doses calculated according to the International Commission on Radiological Protection 60 and 103 publications are 5.6 and 6.4 mSv, respectively. The lifetime-attributable risk of cancer mortality was calculated from the linear-no-threshold model and the ␥-H2AX foci data. This resulted in lifetime-attributable risk values of 1 per thousand and 4 per thousand, respectively, for the patient population under study. Conclusions-␥-H2AX foci as a biomarker for DNA damage indicate that radiation risk estimates according to the linear-no-threshold hypothesis are possibly underestimates. Great care should be taken to minimize and optimize patient radiation exposure.

gamma-H2AX foci response and repair kinetics depend on irradiation conditions and radiation quality, possibly linked to Bystander response.

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This study confirms the reported association of the CHRNA3 locus with nicotine dependence and shows the involvement of two independent DRD2 polymorphisms in nicotine dependence.

Abstract. In the present study, the Á-H2AX assay was investigated as a predictive test for the development of late normal tissue complications. Therefore, phosphorylated histone H2AX (Á-H2AX) foci were scored in peripheral blood T-lymphocytes of gynaecological radiotherapy patients, irradiated in vitro with a high dose rate (HDR) and a low dose rate (LDR) protocol. The G 2 chromatid break assay was used to compare chromosomal radiation sensitivity with DNA doublestrand-break (DSB) repair capacity. Late normal tissue reactions were scored according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 scale. In our analyses, no differences in foci kinetics were found between the non to mild and moderate to severe patient groups after HDR irradiation. Furthermore, no relation was observed between the level of residual Á-H2AX foci and CTC score after LDR irradiation. On the contrary, the number of chromatid breaks was associated with late clinical radiation sensitivity. Comparison of G 2 chromatid break assay data with the residual number of radiationinduced foci after LDR irradiation and repair times after HDR irradiation showed no relationship between the assays. From this study we can conclude that scoring of Á-H2AX foci after in vitro irradiation of isolated T-lymphocytes of patients is not predictive for late radiotoxicity. This applies as well to the assessment of the repair kinetics after an HDR dose as to the determination of the number of residual foci after a LDR dose.