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

Radiation-induced human papillary thyroid cancer (PTC) is associated with c hromosomal inversions that involve the genetic loci H4 and RET on chromosom e 10. Recently, experimental data has shown that these loci lie in very clo se spatial proximity in a high proportion of adult human thyroid cells. App lying the generalized formulation of dual radiation action to this H4-to-RE T geometric distance data, we predict here the radiation dose-response of H 4-RET induction. The predicted H4-RET dose-response has a linear-to-quadrat ic transition dose of similar to7 Gy, suggesting the validity of linear ris k extrapolations to very low doses for H4-RET mediated radiation-induced PT C. In conjunction with A-bomb survivor data, the predicted H4-RET dose-resp onse yields estimates of the number of PTC target cells that are of the ord er of similar to 10(6) to similar to 10(7) cells, i.e. considerably less th an the total number of follicular cells in the thyroid gland.