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, [Ar-40 ions (L = 125 keV mu(-1)), Ne-20 ions (L = 25 keV mu(-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) = CCaLD + BCaD2 (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) x 10(-10); N = (8.8 +/- 1.2) x 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.