On target cell numbers in radiation-induced H4-RET mediated papillary thyroid cancer

Radiation-induced human papillary thyroid cancer (PTC) is associated with chromosomal inversions that involve the genetic loci H4 and RET on chromosome 10. Recently, experimental data has shown that these loci lie in very close spatial proximity in a high proportion of adult human thyroid cells. Applying the generalized formulation of dual radiation action to this H4-to-RET geometric distance data, we predict here the radiation dose-response of H4-RET induction. The predicted H4-RET dose-response has a linear-to-quadratic transition dose of approximately 7 Gy, suggesting the validity of linear risk extrapolations to very low doses for H4-RET mediated radiation-induced PTC. In conjunction with A-bomb survivor data, the predicted H4-RET dose-response yields estimates of the number of PTC target cells that are of the order of approximately 10(6) to approximately 10(7) cells, i.e. considerably less than the total number of follicular cells in the thyroid gland.