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: Fredric J Burns, Moon-shong Tang, Feng Wu, Ernst Schmid
• Journal: Health physics (Health Phys) Vol. 109 Issue 2 Pg. 157-70 (Aug 2015) ISSN: 1538-5159 [Electronic] United States
• PMID: 26107436 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Histones
• Phosphoproteins
• gamma-H2AX protein, rat

Topics

• Animals
• DNA Repair
• Electrons
• Heavy Ions
• Histones (analysis)
• Keratinocytes (chemistry)
• Male
• Neoplasms, Radiation-Induced (etiology)
• Phosphoproteins (analysis)
• Rats
• Rats, Sprague-Dawley
• Regression Analysis
• Skin Neoplasms (etiology)