title: Linking Gamma-H2AX Foci and Cancer in Rat Skin Exposed to Heavy Ions and Electron Radiation.
abstract: This study uses acute doses of three test radiations, [Ar ions (L = 125 keVμ), Ne ions (L = 25 keVμ) 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: YCa(D,L)rat = (NF)2YAX(D,L)keratinocyte (eqn 1), where YCa(D,L) is cancers(rat) at 1.0 y, YAX(D,L) is in vitro gamma-H2AX foci(keratinocyte) , 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 in the delta ray region in between the ion tracks (second term): YCa(D,L) = CCaLD + BCaD (eqn 1a). Parameters quantified include: CCa = 0.000589 ± 0.000150 cancers-micron[rat(kev)Gy]; BCa = 0.0088 ± 0.0035 cancers(ratGy), F = (8.18 ± 0.91) × 10; N = (8.8 ± 1.2) × 10 and (NF)2 = 0.036 ± 0.006 cancer keratinocyte(rat H2AX foci). 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) predicted 1.0 cancer(rat) at 1 y.
authors.affiliation: *NYU School of Medicine, Department of Environmental Medicine, 57 Old Forge Road, Tuxedo, NY 10987; †University of Munich, Institute of Cell Biology, Munich, Germany.
authors.forename: Fredric J
authors.initials: FJ
authors.lastname: Burns
authors.forename: Moon-shong
authors.initials: MS
authors.lastname: Tang
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
authors.forename: Ernst
authors.initials: E
authors.lastname: Schmid
mesh_terms: D000818:Animals; D004260:DNA Repair; D004583:Electrons; D020450:Heavy Ions; D006657:Histones / Q000032:analysis*; D015603:Keratinocytes / Q000737:chemistry; D008297:Male; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D010750:Phosphoproteins / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D012878:Skin Neoplasms / Q000209:etiology*
chemical_list: D006657:Histones; D010750:Phosphoproteins; C577575:gamma-H2AX protein, rat