Linking Gamma-H2AX Foci and Cancer in Rat Skin Exposed to Heavy Ions and Electron Radiation

This study uses acute doses of three test radiations, [(40)Ar ions (L = 125 keVμ(−1)), (20)Ne ions (L = 25 keVμ(−1)) and electron radiation] to examine a potential quantitative link between rat skin cancer induction and gamma-H2AX foci in rat keratinocytes exposed in vitro to radiations with comparable L values. Theory provided a testable link between cancer yield and gamma-H2AX foci yields: Y(Ca)(D,L)rat(−1) = (NF)2(−1)Y(AX)(D,L)keratinocyte(−1) (eqn 1), where Y(Ca)(D,L) is cancers(rat) (−1) at 1.0 y, Y(AX)(D,L) is in vitro gamma-H2AX foci(keratinocyte) (−1), D is radiation dose, L is linear energy transfer, N is irradiated keratinocytes in vivo, and F is the error rate of end joining. An explicit expression for cancer yield was derived based on cancers arising in the ion track region in proportion to D and L (first term) and independently in proportion to D(2) in the delta ray region in between the ion tracks (second term): Y(Ca)(D,L) = C(Ca)LD + B(Ca)D(2) (eqn 1a). Parameters quantified include: C(Ca) = 0.000589 ± 0.000150 cancers-micron[rat(kev)Gy](−1); B(Ca) = 0.0088 ± 0.0035 cancers(ratGy(2))(−1), F = (8.18 ± 0.91) × 10(−10); N = (8.8 ± 1.2) × 10(7) and (NF)2(−1) = 0.036 ± 0.006 cancer keratinocyte(rat H2AX foci)(−1). Verification of eqns (1) and (1a) and the constancy of F support the hypothesis that end-rejoining errors play a major role in radiation carcinogenesis in rat skin. Cancer yields per rat were consistently predictable based on gamma-H2AX foci yields in keratinocytes in vitro such that 27.8 H2AXfoci(keratinocyte)(−1) predicted 1.0 cancer(rat)(−1) at 1 y.